Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer

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AUA Comment on Proposed Decision Memo on Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer

The American Urological Association (AUA), which represents 90 percent of the practicing urologists in the U.S, is pleased to comment on the Proposed Decision Memo on autologous cellular immunotherapy treatment of metastatic prostate cancer. The long-standing mission of the AUA is to promote the highest standards of clinical urological care through education, research, and formulation of health care policy. The public health burden of urological disease in the United States is large and growing. Urologists are the specialists who most often diagnose and treat prostate cancer, the second leading cause of cancer deaths among men in the U.S. Prostate cancer will newly affect 217,000 men in the U.S. this year and result in nearly 32,050 deaths according to the American Cancer Society. ¹ It is estimated that seventy-five percent (75%) of prostate cancer patients are Medicare beneficiaries.

The AUA is a strong advocate for evidence-based medicine and the importance of well-designed randomized clinical trials to develop clinical evidence of the effectiveness of drugs, devices, and procedures. We strongly support the Proposed Decision Memo that finds the evidence is adequate to conclude the use of autologous cellular immunotherapy treatment sipuleucel-T; PROVENGE® improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication under Medicare.

Two randomized controlled trials have now been completed that yield consistent findings of a statistically significant survival benefit for Provenge immunotherapy among men with castration-resistant metastatic prostate cancer. In the pivotal IMPACT trial which enrolled 512 men, Provenge provided a survival prolongation of 4.1 months. ² Provenge was administered over one month and the majority of the survival benefit was not consumed by administration of the treatment or management of toxicity. Most adverse events were grade 1 or 2 and resolved within 48 hours. Only three patients in the Provenge arm of the IMPACT trial were unable to receive all three infusions because of adverse events. One month of therapy conferred a 4.1 month survival benefit. In contrast, six months of docetaxel chemotherapy is required to provide a 2.4 month survival benefit. This benefit to burden ratio overwhelmingly favors Provenge.

Add to this the time (sometimes associated with hospitalizations) required to manage the toxicity of chemotherapy and the benefit to burden ratio is further amplified. Provenge is unique as a treatment for far advanced disease where the survival advantage is not consumed by the time required for delivery of treatment and management of treatment toxicity. As approximately 50 percent of patients in both arms of the IMPACT trial received docetaxel after the study treatment, treatment with Provenge did not preclude subsequent therapies.

Provenge is the first active cellular immunotherapy agent that has been demonstrated to be effective against malignant disease. It represents a new treatment class and a fourth modality that can be brought to bear against prostate cancer. Urologists hope it promises to be the foundation for a gentler, more effective therapy than is now available for metastatic castrate-resistant disease. It could be a platform for the treatment of other malignancies.

The results of the IMPACT trial support the conclusion that Provenge significantly improves overall survival in patients with asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer. The IMPACT trial permits the conclusion that Provenge avoids the adverse effect burden of docetaxel and carbaxytaxol chemotherapy, the only other FDA-approved agents for metastatic castrate-resistant prostate cancer, as described in Berthold, Pond, et. al. ²

Provenge is a break-through product that fills an unmet need for patients with castration-resistant prostate cancer providing a significant increase in survival without severe side-effects. Autologous cellular immunotherapy may broaden the horizon of cancer treatment in general.

Again, the American Urological Association strongly supports the Proposed Decision Memo. Thank you for your attention to the concerns of America’s urologists.

Steven M. Schlossberg, M.D.
Chair, Health Policy Council
American Urological Association

References
1. American Cancer Society. How Many Men Get Prostate Cancer? 2010. Online at ww.cancer.org/Cancer/ProstateCancer/OverviewGuide/prostate-cancer-key-statistics. Accessed November 10, 2010.

2. Berthold, D.R., Pond, G.R., Soban, F., de Wit, R, et al: Docetaxel Plus Prednisone or Mitoxantrone Plus Prednisone for Advanced Prostate Cancer: Updated Survival in the TAX 327 Study. J Clin Oncol 2008; 26:242.

For further inquiries, contact:
Inger Saphire-Bernstein
Manager of Regulation
American Urological Association
1000 Corporate Boulevard
Linthicum, Maryland 21090
Phone: 410-689-3745
Email: Isaphire-bernstein@auanet.org

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I am shocked by the apparent acceptance of Provenge to reportedly delaydeath of Pca patients for about four months. This at a cost of $90,000. I belive that there should be a body of people (doctors) that can deny treatment payments from Medicare for this type expense.I understand that Medicare can not deny such payments.Too bad that Dendreon has invested Billions. I believe we as a nation must get real about making these sort of medical/health decisions. I do not think that in this case the patient should be given or asked to make a choice.

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Louis Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
Mail Stop S3-02-01
7500 Security Blvd.
Baltimore, MD 21244
Re:Response to Draft National Coverage Decision for sipuleucel-T

Dear Dr. Jacques,

Our medical group, Prostate Oncology Specialists in Marina del Rey, CA, strongly supports the recently published National Coverage Determination for sipuleucel-T which concluded that sipuleucel-T is reasonable and necessary for men with castrate resistant prostate cancer.

However, for the current on-label indication, we do remain concerned that the broad coverage language which mirrors the FDA indication statement will not be sufficiently detailed for the regional contractors to implement. To that end, we have carefully reviewed the FDA indication statement, as well as the clinical trial criteria for the Phase 3 pivotal IMPACT trial, and suggest that the following four criteria would be comprehensive and appropriate. These criteria could be objectively implemented and audited by your contractors in both hospital outpatient and office settings.

1. Diagnosis of Prostate Cancer. The diagnosis of prostate cancer is readily determined by physicians, and therefore should not require further specification. While a histologic diagnosis is frequently obtained at the time of initial diagnosis, it should not be required, as it may be difficult to obtain at the time of metastatic disease, which often occurs many years following the initial diagnosis and when care may be in the hands of a physician who did not make the initial diagnosis. Furthermore, the occasional patient may be diagnosed with metastatic prostate cancer based on a highly elevated prostate specific antigen level in the peripheral blood in combination with a characteristic evidence of metastases on imaging studies. This is widely accepted as consistent with the diagnosis. For both of these reasons, a requirement for a histologic diagnosis could lead to unnecessary biopsy procedures or unnecessarily exclude appropriate patients. Since the majority of patients with metastatic disease no longer have their prostate in place, a tissue diagnosis requires biopsy of a metastatic site, typically retroperitoneal lymph nodes or bone, which is invasive and associated with some risk to the patient.

2. Evidence of metastatic disease. The presence of metastatic disease is readily ascertained and documented by physicians. Specification of the modality by which metastatic disease is determined should not be necessary, and would not allow for technological advances in the detection of metastatic disease.

3. Castrate resistant disease, as determined by current or historical evidence of disease progression in the setting of medical or surgical castration. Once a patient’s cancer becomes castrate resistant, it remains castrate resistant. Therefore, the diagnosis of castrate resistance need not be made more than once for a particular patient. Historical evidence of castrate resistance should be sufficient for coverage, just as it is sufficient for decision making in routine clinical practice. Furthermore, we urge caution regarding the extent to which the technologies used to determine disease progression are specified in the coverage rules, as biomarker and imaging assays for disease activity continue to evolve.

4. Either asymptomatic or mildly symptomatic prostate cancer defined as not currently taking narcotics for cancer related pain. Most men diagnosed with castrate resistant prostate cancer are initially quite functional and typically do not have more than minimal pain due to their disease. Limiting coverage for sipuleucel-T to men who are not receiving narcotics for cancer related pain would be the most logical and practical approach and would be consistent with our clinical use of sipuleucel-T. Likewise, by specifying non-coverage only for those patients who take narcotics for cancer-related pain, the coverage would match the description of the study entry criteria on the FDA label for sipuleucel-T, and ensure that men taking narcotics for other reasons could still receive treatment.

Specification of these four criteria should be sufficiently precise for regional contractors to use for coverage decisions. The language of the National Coverage Determination should clarify that additional criteria, and specifically the large number of technical eligibility criteria for the sipuleucel-T pivotal trial should not be used. In the final National Coverage Determination, we would recommend that Appendix D, which lists the eligibility criteria for the IMPACT trial, be removed. If CMS wants to provide readers with a publicly available resource from which to learn more about Provenge, it could be replaced by a copy of the FDA package insert or the primary publication in the New England Journal of Medicine.

The appendix as presented poses a serious risk that CMS’ intent at the national level, which appears to be to appropriately cover patients who meet the on-label indication statement on the FDA label, will be undermined at the local level if MACs apply criteria that were used for carefully controlled randomized research studies rather than follow the coverage language. Under such a scenario, physicians will face uncertainty about reimbursement. But far more importantly, patients with a life-threatening condition could be denied a treatment that has, as the Medicare Evidence Development & Coverage Advisory Committee (MedCAC) votes attest and the FDA concluded, significantly prolongs overall survival with manageable and self-limited toxicity.

In summary, specification of the four criteria noted above would provide clear guidance for the regional contractors on how to implement coverage for the label indication. Removal of Appendix D would also help ensure that coverage is uniform across the country for men with metastatic prostate cancer, and that everywhere men who meet the indication statement can have the chance to benefit from this important new biologic treatment advance.

Sincerely,

Mark Scholz MD, Richard Lam MD & Patricia Chang MD

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Louis B. Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
Mail Stop C1-09-06
7500 Security Boulevard
Baltimore, Maryland 21244-1850

Dear Dr. Jacques:

Thank you for the opportunity to comment on the Centers for Medicare and Medicaid Services’ (CMS) national coverage decision memo (NCD) for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer CAG-00422N). America’s Health Insurance Plans (AHIP) is the national association representing nearly 1,300 health insurance plans providing coverage to more than 200 million Americans. We are pleased to submit these comments on behalf of our members.

General Comments
AHIP supports CMS's efforts to ensure that all Medicare beneficiaries receive the most effective and appropriate treatments based on current and valid scientific evidence. We support CMS’s efforts to review all current and available clinical evidence in order to determine appropriate coverage for treatments and procedures that are shown to be safe, effective, and improve the health and health outcomes of Medicare beneficiaries. AHIP and our member plans support the development of new and innovative treatments and acknowledge the promise of autologous cellular immunotherapy as a treatment for metastatic prostate cancer.

Our members concur with CMS that Medicare coverage for the use of autologous cellular immunotherapy treatment- sipuleucel-T; PROVENGE® should be limited to beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and those populations who are most likely to achieve benefit. For example, consideration should be given to populations who have:

• ECOG (Eastern Cooperative Oncology Group) performance status 0-1^[i]; and
• No visceral metastasis^[ii], and
• Life expectancy of greater than 6 months^[iii]; and
• Appropriate serum prostate-specific antigen (PSA) and testosterone levels; and
• Progressive disease based on imaging studies or PSA measurements; and
• No treatment within the previous 28 days with systemic glucocorticoids, external-beam radiation (EBRT), surgery, or systemic therapy for prostate cancer (except medical or surgical castration); and
• No chemotherapy within the previous 6 months.

When determining coverage for autologous cellular immunotherapy, CMS should compare the effectiveness of this treatment against the other six available treatments for this type of prostate cancer. In addition, the Food and Drug Administration (FDA) has determined that due to reports of cerebrovascular events in patients undergoing therapy with Provenge, Dendreon Corporation, the manufacturers of the only FDA-approved autologous cellular immunotherapy (Provenge), must comply with post-marketing requirements and perform a registry-based study to assess the risk of these events in 1,500 patients with prostate cancer who receive Provenge. Given these events, CMS should carefully analyze the comparative benefits and harms of this treatment outside clinical studies, including the results from the required registry, to determine the potential value for Medicare beneficiaries.

Thank you for the opportunity to comment on this important issue.

Sincerely,

/s/
Carmella Bocchino
Executive Vice President
Clinical Affairs and Strategic Planning

[i] National Comprehensive Cancer Network. Version 1.2011, 12/13/10.

[ii] ibid

[iii] ibid

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I want to thank CMS for proposing a very reasonable on-label coverage category. The added caveat for leaving off-label coverage up to contractors was very welcome as well. I hope CMS will stick firmly to those proposals.

For anyone who has looked at Provenge closely, the larger beneficial prospects for treatment will come if, and I expect it will, when the evidence accumulates supporting Dr. Dan George's contention that the actual survival benefit for the 'tested' population somewhere in the 8-14 month range.

Moreover, preliminary results from the "PROTECT" trial indicate what has been suggested from the beginning of Provenge trials. That earlier treatment in the disease process would be beneficial.

Finally, contrary to what many people believe, Provenge has been shown to be cost effective when all treatment-related medical costs are compared with competitive treatments (e.g. the Millman Report), and, the quality of life factor is far superior to most any treatment for prostate cancer from the middle stages on.

The physician commenters who recommended more restrictive coverage appeared to have both a limited knowledge and understanding of Provenge.

While I understand Dr. Lynn's concern, as one example, her comments seemed excessive as they applied to what appears to be a small subset of the prospective patient population. Anyone who has done research on rising health care costs in recent years knows that part of the problem is what Dr. Gawande (New Yorker Magazine), among many others, has referred to as the role of 'entrepreneurial' physicians in rising health costs.

However, if I may use an awkward metaphor, her approach risks a kind of 'throwing the baby out with the bath water' situation.

Personally I would agree that Provenge patient data should be collected, organized and monitored including any indications that Provenge will benefit patients at an earlier disease stage. Hopefully, the Provenge process will be seen as part of the larger effort to develop immunotherapy treatments for a variety of cancers which will provide increasing benefits both clinically and financially in the future. I would like to think CMS would play in active role in that effort.

And please don't forget, Vietnam veterans suffer from increased rates of prostate cancer. Unfortunately, the Iraq wars in particular raise that and other issues due to chemical weapons exposure.

Thank you for your time.

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My husband and I feel that Dendreon is the very best choice for Prostate Cancer available to the American people at this time, and pray it will be available as soon as is possible. Their product is a blessing to All men in need of this great new procedure. To be almost painless at the end of one's life, is a God-Given Gift that will be accepted with thanks. To be able to share more months and even more years with one's family is priceless.

Please provide the finacial needs for all, those who are or are not able the pay for it themselves, and FULLY allow Medicare to pay for it in the very near future.

Sincerely,

Gen.and Mrs. Richard B, Spear, USAF, Ret.

From the bottom of our hearts we would thank you for doing the right thing and fully approve Dendreon and make available in the very near future..

B/Gen. and Mrs. Richard B. Spear, USAF,Retired.

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As a leading national patient advocate organization for men in the United States, ZERO supports the proposed decision by CMS regarding coverage of autologous cellular immunotherapy treatment of metastatic prostate cancer.

We are encouraged by this decision as it represents an entirely new way of treating diseases in general, and cancer specifically. Not only will this new treatment represent hope for prostate cancer patients who have run out of options, but it will usher in a new wave of research that will revolutionize the way we as a society treat patients.

While we are encouraged by the promise and hope this decision will bring, we are concerned about the use of clinical trial eligibility criteria as coverage criteria. This would potentially restrict the use of the treatment to a smaller subset of individuals rather than all that might benefit from it. We hope that clarification will be offered to ensure that proper criteria are used so that men who need the treatment and qualify to receive are able to benefit from it.

Thank you for you time.

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Dr. Donald Berwick
Administrator
Centers for Medicare & Medicaid Services
Mail Stop 314G? 200 Independence Ave. S.W.?
Washington, D.C. 20201?
Donald.Berwick@CMS.hhs.gov

Dear Dr. Berwick:

The Large Urology Group Practice Association (LUGPA) was established in order to provide urologists practicing within large groups the best methodology to access resources, technology and management tools that will provide the best possible care for our patients. Today, LUGPA membership represents ~2000 practicing US urologists. Our mandate has always been to provide the best possible care for our patients, according to US Food and Drug Administration approval and in conjunction with the most widely accepted clinical guidelines, as reviewed by our national organizations and our expert practioners.Thus, the LUGPA Executive Board is writing to you in support of the Center for Medicare and Medicaid Services’ (CMS) proposed decision for sipuleucel-T (Provenge), which stated that “the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication.”

We are concerned, however, that the broad language of this draft decision memorandum does not provide enough detail to for physicians and their local Medicare contractors to be clear on how this coverage is to be implemented. We have reviewed the recent letter from Drs. Kantoff, Higano, Petrylak, Schellhammer, and Small and concur that the criteria suggested within that letter could be objectively implemented and should become the basis for CMS’ final NCD language. A diagnosis of prostate cancer, evidence of metastatic disease, evidence of castration-resistant disease, and the absence of narcotics for cancer-related pain clearly line up with FDA’s labeled indication of asymptomatic or minimally symptomatic, metastatic, castrate-resistant prostate cancer. Any further restrictions or limitations on access should be considered unduly burdensome for patients and physicians alike in the provision of medically necessary services that have been established as “reasonable and necessary”.

In April of last year, the Center for Biologics Evaluation and Review (CBER) of FDA approved Sipuleucel-T as the first-ever autologous cellular immunotherapy for solid tumor malignancy, specifically for prostate cancer patients. This drug prolongs survival with minimal impact upon quality of life, and requires a very short duration of therapy, approximately 30-45 days. While the approval of this novel biologic marked a significant advancement in the treatment of prostate cancer, fulfilling an unmet clinical need by offering treatment to patients with castration resistant prostate cancer who are either asymptomatic or minimally symptomatic, and not yet appropriate for chemotherapy – we believe the approval represents much more than that. It marks the dramatic advancement of an era of personalized medicine that will potentially be used in the treatment of other malignancies as well. These products create an entire class of biologics called active immunotherapies to fight cancer, harnessing key components of the immune system to engage specific responses against cancer cells, while minimizing related clinical toxicities, and thus maintaining patient quality of life.

Last year, in the United States alone, prostate cancer was responsible for the deaths of almost 32,000 men. We recognize the devastating impact of advanced prostate cancer on men, their families, and their communities and urge CMS to allow these citizens access to all innovative and new treatment options, such as Provenge. The LUGPA membership has joined with the Prostate Health Education Network (PHEN) and the National Council of Black Churches in working together to end the African American Cancer Disparity during this year’s Father’s Day rally throughout the United States. We are committed to offering improved screening services as well as advanced prostate cancer therapies to all underserved populations in the US affected by urologic malignancies.

We urge CMS to support the FDA labeled indication for Provenge, and not allow for unnecessary barriers to prevent our patients from receiving this new drug. In the final NCD policy, we ask CMS to be clear to support payment for the FDA approved indication of Provenge and ensure that men with metastatic, castrate-resistant prostate cancer have access to Provenge per its FDA-approved label.

The LUGPA executive board would welcome the opportunity to directly meet with you and any interested committees of CMS in order to explore the administration, utilization and reimbursement of new treatments for the patients we treat, and look forward to helping you develop objective data on this and all other issues impacting the care of patients with genitourinary disease.

Sincerely,

Raoul S. Concepcion, M.D., F.A.C.S.
President
Large Urology Group Practice Association

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April 28, 2011

BY ELECTRONIC DELIVERY

Louis B. Jacques, MD
Director, Coverage and Analysis Group
Medicare Drug & Health Plan Contract Administration Group
Centers for Medicare & Medicaid Services
Mail Stop S3-02-01
7500 Security Boulevard
Baltimore, MD 21244

Re: Proposed Decision Memo for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (CAG-00422N)

Dear Dr. Jacques:

The Association of Community Cancer Centers (ACCC) appreciates this opportunity to comment on the Centers for Medicare & Medicaid Services’ (CMS) proposed decision memorandum for autologous cellular immunotherapy treatment of metastatic prostate cancer.¹ ACCC is a membership organization whose members include hospitals, physicians, nurses, social workers, and oncology team members who care for millions of patients and families fighting cancer. ACCC’s more than 900 member institutions and organizations, when combined with our physician membership, treat 60 percent of all U.S. cancer patients.

ACCC is committed to ensuring that patients have access to the most appropriate treatments and diagnostic tools needed to prevent, diagnose, and treat cancer. We strongly support CMS’s proposed decision to cover autologous cellular immunotherapy, sipuleucel-T (marketed as PROVENGE®) for its Food and Drug Administration (FDA) approved indication of treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. By definition, patients who have this type of prostate cancer have few or no other treatment options; their disease has continued to progress despite receiving medical or surgical castration therapy. Sipuleucel-T offers new hope for these patients, and we urge CMS to finalize this decision and issue a national coverage determination (NCD) to allow Medicare beneficiaries the option to benefit from this innovative biological product.

We also support CMS’s proposal to allow its local contractors to determine coverage of off-label uses of sipuleucel-T. At present, there is little evidence on any off-label uses, but as data are gathered and analyzed, this approach will give contractors “flexibility to determine local coverage without the need to reconsider an NCD.”² This is consistent with the Medicare statute, which recognizes as “medically accepted indications” of drugs or biologicals used in an anticancer chemotherapeutic regimen certain uses supported by one or more citations in certain authoritative compendia or peer-reviewed medical literature.³ Congress enacted this provision to ensure that Medicare coverage of cancer therapies keeps up with changes in the standard of care, and CMS’s proposed decision supports this goal. ACCC shares CMS’s belief that “preserving local contractors’ ability to quickly broaden coverage within their jurisdictions will hasten beneficiary access,”⁴ and we commend the agency’s proposed decision regarding coverage of off-label uses of sipuleucel-T.

Finally, we urge CMS to provide clear instructions in the final decision memorandum and the NCD that contractors may not restrict coverage for sipuleucel-T when used for its FDA-approved indication. We have heard that some Medicare Administrative Contractors (MACs) have imposed coverage requirements for sipuleucel-T that are not consistent with the FDA-approved indication. For example, some MACs have required beneficiaries to meet the pre-approval clinical trial inclusion and exclusion criteria in order for sipuleucel-T to be covered. These criteria include requirements that a patient have a prostate-specific antigen (PSA) score above 5 ng/mL, have subsequent PSA testing after developing castrate resistant prostate cancer, or that the provider submit histologic documentation of the patient’s diagnosis of prostate cancer.

These requirements may have been appropriate for the pre-approval clinical trials, but none of these requirements is valid for coverage of sipuleucel-T when used for the FDA-approved indication. When the FDA approved the Biologics License Application (BLA) for sipuleucel-T, it determined that the biological was safe and effective for all patients with the condition described in the approved indication. Medicare now should cover the biological product for any beneficiary who meets that indication. In addition, if CMS or its contractors were to impose such requirements, patients would be subjected to additional procedures that have no benefit at this stage of their disease. PSA test results, for example, may not reflect disease progression at the time the patient is prescribed sipuleucel-T. Likewise, additional confirmation of the diagnosis of prostate cancer is absurd when the patient would qualify for treatment with sipuleucel-T only after other treatments had failed and patients have progressed to the metastatic castrateresistant state.

CMS should specify in the final decision that the only requirements for coverage are that the patient satisfy each element of the FDA-approved indication, and the agency should instruct its contractors not to apply narrower criteria. CMS also should remove the description of the clinical trial inclusion criteria, listed at Appendix D of the proposed decision memorandum, from the final decision to avoid confusion about the coverage criteria and prevent contractors from needlessly denying beneficiaries access to an appropriate therapeutic option.

ACCC appreciates the opportunity to submit these comments. We would be pleased to answer any questions. Please contact Matt Farber at 301-984-9496, ext. 221 if ACCC can be of any assistance.

Sincerely,

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Comment to CMS on Provenge National Coverage Determination:

This therapy is a critically important milestone in the treatment of prostate cancer for all men. It is especially important to the many men at high risk, many of whom are typically diagnosed at late stages of the disease.

The positive impact on survivability will be immeasurable. As such, I support the CMS current determination with regard to Provenge, and strongly urge CMS to make Provenge available to Medicare beneficiaries in its final determination.

Sincerely,
Mark Kennedy

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I would strongly recommend that CMS approve Provenge for it's FDA approved use in prostate cancer. Not only is this drug a breakthrough treatment for this indication,but with it's limited side effects represents a new benign way to treat cancer.

This new treatment represents the best of American Science and demonstrates why people all over the world come here for treatment and look to us for breakthrough medicines. History will record all those individuals that enable this breakthrough and benign treatment as not only on the right side of science,but also demonstrating the integrity to do the RIGHT thing.

Remember your integrity and your treatment of your fellow man is all you leave behind in your life .

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Frankly, many of us were concerned and fearful this day would not come. It is with excitement that I add my voice and express my support for the CMS proposed decision that states Provenge improves health outcomes for men with asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer and is reasonable and necessary.

Many of us from Us TOO as well as numerous others attended and shared our comments at the MEDCAC meeting. In addition, nearly 4,000 people signed a petition which I will be forwarding to the CMS offices. The petition states, “We the undersigned, call on CMS administrator Berwick to stop potentially limiting access to FDA approved cancer treatments, such as Provenge, for men fighting advanced prostate cancer. Instead we want him to demonstrate his commitment to patients, their families and health care professionals by providing his full support for appropriate unrestricted access and coverage by Medicare.”

Thank you for this decision, there are thousands who will soon be allowed fair and equal access to a new arrow in their quiver they fight for their lives.

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Dear Doctor Berwick,

As a Representative of the state of Georgia, I would like to congratulate CMS on their recent decision to support patients of advanced prostate cancer by covering Provenge. Since my days as a state senator, I've been committed to making sure that citizens in the state of Georgia have proper access to lifesaving cancer medications and Provenge represents the forefront of new personalized medications that will dominate the rest of the century and change the way we treat patients. The inclusion of Provenge will also increase jobs in my district due to the creation of a Provenge factory in the 13th district of Georgia. I urge CMS not place restrictions that will block access to treatment. It is critical that patients and doctors have access to Provenge without restrictions and limitations.

Thank you for your consideration,

Congressman David Scott.

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I strongly support The Centers for Medicare and Medicaid Services (CMS) draft determination that the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication under 1862(a)(1)(A) of the Social Security Act (the Act).

In addition, I recommend that the final national coverage determination removes any ambiguity between the clinical trial enrollment criteria and the FDA approved label to insure access to Provenge for the men in need.

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April 28, 2011

BY ELECTRONIC DELIVERY

Louis Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare & Medicaid Services
Mail Stop S3-02-01
7500 Security Blvd.
Baltimore, MD 21244

Re: Proposed Decision Memorandum for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (CAG-00422N)

Dear Dr. Jacques:

The Biotechnology Industry Organization (BIO) appreciates this opportunity to comment on the Centers for Medicare and Medicaid Services’ (CMS) Proposed Decision Memorandum for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer.¹ BIO is the largest trade organization to serve and represent the biotechnology industry in the United States and around the world. BIO represents more than 1,100 biotechnology centers, academic institutions, state biotechnology centers, and related organizations in the United States and in more than 30 other nations. BIO members are involved in the research and development of health care, agricultural, industrial and environmental biotechnology products.

In particular, many of our members are involved in the research and development of cancer therapies and play a critical role in delivering treatments that both prolong life and reduce the burden of disease for cancer patients worldwide. As such, BIO has a particular interest in CMS actions that may impact patient access to novel therapies.

BIO supports CMS’s proposed decision for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer as it addresses a number of issues outlined in our initial comment letter to CMS.² Importantly, BIO is pleased that the proposed decision preserves the ability for physicians and their patients to make the treatment determination that is optimal for their situation. As we have commented previously, BIO strongly urges CMS to follow sound principles of evidence-based medicine in formulating coverage policies.

BIO continues to be concerned by the new precedent of opening a National Coverage Analysis (NCA) on a recently-approved therapy. When CMS initiates an NCA on a technology, its action may be perceived by Medicare contractors, other payers, and the investment community as a sign they should withhold coverage or support until the NCA is concluded. These actions may in turn curtail labeled and appropriate uses of a Food and Drug Administration (FDA) approved therapy, particularly before the medical community has the opportunity to develop experience with the labeled use of the therapy. BIO continues to assert that there should be no question that an FDA-approved therapy should be covered for the patients and conditions indicated on its label.

BIO appreciates the opportunity to submit these comments. We urge CMS to finalize the proposed decision as quickly as possible. Please contact me at (202) 962-9220 if you have any questions regarding these comments. Thank you for your attention to these very important matters.

Respectfully submitted,

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At some point CMS, as will all of us, will have to face the question: When is the cost of a treatment, for what small benefit it provides, not worth the price we will have to pay in the form of cuts to other more beneficial services or loss of coverage entirely? If not $100,000 for four months of additional survival, will it be at $1,000,000 for one month? $100,000 will pay for the medical costs of Medicaid benefits for about 24 Minnesotans for a year. Even more concerning will be the treatments that marginally reduce the rate of decline from a chronic disease for $100,000 per month but would go on for years. As hard as it may be to accept, a cutoff based on cost per Quality Adjusted Life Years is needed.

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April 25, 2011

Louis B. Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
Mail Stop S3-02-01
7500 Security Boulevard
Baltimore, MD 21244

Re: Comments on Proposed Decision Memo for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (CAG-00422N)

Dear Dr. Jacques,

On behalf of Dendreon Corporation (Dendreon), I applaud the Centers for Medicare & Medicaid Services’ (CMS’) proposed decision that the “evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication under 1862(a)(1)(A) of the Social Security Act.” (1) I appreciate that CMS reached this conclusion after employing a rigorous evidence-based process that included public comments, an extensive review of the clinical evidence by the Agency for Healthcare Research and Quality (AHRQ), and a day-long Medicare Evidence Development & Coverage Advisory Committee (MedCAC) meeting where votes were taken.

This proposed decision follows on the conclusion of the Food and Drug Administration’s (FDA’s) Center for Biologics Evaluation and Research (CBER) that PROVENGE is safe and effective for this same indication. PROVENGE was approved by FDA under a Biological License Application (BLA) on April 29, 2010, and has been granted a National Drug Code (30237-8900-06).

I also endorse CMS’s proposed decision that the regional Medicare Administrative Contractors (MACs) will determine coverage of PROVENGE for off-label indications. As I stated at the MedCAC meeting, there are no data to support the off-label use of PROVENGE. Your decision to leave determination of non-coverage for off-label uses at the discretion of the MACs demonstrates an appreciation that the clinical data on PROVENGE will continue to evolve over time. If the science develops to support the use of PROVENGE in new indications, your decision will permit Medicare beneficiaries to have access to PROVENGE without having to wait the nine or more months for a national coverage analysis reconsideration.

I also want to re-articulate Dendreon’s commitment to conducting follow-up analyses of PROVENGE utilization and outcomes through the treatment registry that we have set up at the request of FDA. The data from the registry will be analyzed by a steering committee of prostate cancer thought leaders, and results will be published in the peer-reviewed literature. The analyses will provide deeper insights into the outcomes of patients treated with PROVENGE outside of clinical trials, and will provide a better understanding of the outcomes of sub-groups, such as African-American patients, who in the clinical trials appeared to experience a larger benefit from the biological than did the overall treated population.

We do have some concerns with how the MACs may operationalize the proposed National Coverage Determination (NCD), which mirrors the indication statement on the FDA label. We have already learned of circumstances where MACs have inappropriately applied factors unrelated to clinical efficacy, such as some of the clinical trial eligibility criteria that were in place for the assessment of secondary endpoints, rather than use the characteristics described in the FDA label. These events were occurring before the proposed NCD was published, but we are concerned that a continuing discordance between the stated national coverage policy and the local MAC policies may be perpetuated if the final national coverage decision includes the Appendix D that appears in the proposed decision memorandum.

Appendix D presents the eligibility criteria for the Phase 3 pivotal IMPACT trial of PROVENGE. This information is already widely available from the published clinical study, the AHRQ technology assessment, and the drug label, so physicians and MACs already have access to it for use in understanding the clinical research studies that led to the approval of PROVENGE. However, the eligibility criteria for this trial are not of direct relevance to CMS’ proposed coverage decision, as that matches the FDA indication statement, which already takes into account the practical nature of applying the IMPACT trial findings to a clinical population of patients. If CMS includes Appendix D in the final decision, some MACs could be misled to think that eligibility criteria for a randomized controlled trial are the same as coverage criteria for the Medicare program, even though they clearly are not.

To clarify further, eligibility criteria for clinical trials serve many methodologic purposes that are not relevant to the determination of which patients should be expected to benefit. For example, in IMPACT, the pivotal Phase 3 clinical trial of PROVENGE, some eligibility criteria were in place because of secondary endpoints that were of interest to researchers and the FDA, but have no bearing on the robust finding that PROVENGE improves overall survival in the on-label population. The distinction between clinical trial eligibility criteria and appropriate parameters for the on-label use of PROVENGE is one appreciated by the FDA, and is the reason why the indication statement does not re-articulate those eligibility criteria that do not translate from clinical research to clinical care.

This same distinction may not be clear to the MACs, which are currently applying some of the trial eligibility criteria to some patients, albeit inconsistently across regions. As a result, some patients who meet the conditions described in the indication statement are being denied access to treatment. To avoid further misunderstanding about the relationship between the trial eligibility criteria and the FDA-approved use of PROVENGE, we recommend that the final decision memorandum not list the eligibility criteria in a separate appendix. Instead, the eligibility criteria should be discussed in the “Evidence Summary” section of the decision memorandum, where the trial’s design and results are discussed.

Below we list some of the problems that have arisen or could arise when MACs endeavor to apply clinical trial eligibility criteria as coverage criteria. These include both clinical and administrative issues. Both can be addressed by providing clear instructions in the NCD about the criteria for coverage of PROVENGE, as well as clarifying that certain clinical trial criteria should not be used in determining coverage. This will help ensure beneficiary access to PROVENGE without disparities across regions.

• Definition of “castrate resistance.” Some MACs have misconstrued “castrate resistance” as something that must be diagnosed at the time of treatment with PROVENGE. In fact, “castrate resistance” is a disease state that patients pass into and never leave. A patient is “castrate” if he has had an orchiectomy or has received regularly scheduled injections of a luteinizing hormone releasing hormone (LHRH) agonist (e.g., leuprolide acetate) or an LHRH antagonist (e.g., degarelix). Testosterone levels will be low in this situation; they are not routinely checked in clinical practice. Furthermore, a patient’s cancer has become “castrate resistant” when he has evidence of disease progression (e.g., by rising prostate specific antigen [PSA] or progression on imaging) following castration therapy. The requirement by some MACs for two sequential rising PSA tests at the time of evaluation for PROVENGE lacks clinical insight into the “castrate resistant” disease state, and also is inconsistent with the eligibility requirements for the IMPACT trial. IMPACT only required documentation of castrate resistance at some point prior to trial entry. The NCD should state that patients should be castrate resistant, meaning that at any point in the past or currently they have evidence of disease progression in the setting of castration therapy. The NCD should clarify that current evidence of progression by PSA or other methods is not a requirement for coverage. To allow for technological advance, I would encourage you to consider that the NCD not specify a particular method (e.g., PSA or a specific imaging modality) by which disease progression in the setting of castrate resistance is documented.
• PSA level. The IMPACT trial required patients to have a minimal PSA level of 5 ng/mL, but this criterion was in place to allow for the assessment of PSA kinetic endpoints, not for any reason related to the safety or efficacy of PROVENGE. Instituting a minimum PSA requirement for coverage would not make clinical sense, as it would exclude some patients with castrate resistant prostate cancer, including those with tumors that do not secrete PSA. In subset analyses of the IMPACT trial, patients with PSA levels below the median experienced survival prolongation, which trended towards greater benefit than those with PSA levels above the median (Kantoff et al., N Engl J Med, 2010, Figure 3). There is therefore no suggestion that patients with lower PSA levels will not benefit from sipuleucel-T. The NCD should state that PROVENGE will be covered regardless of a beneficiary’s PSA level.
• Life expectancy. Life expectancy is sometimes included as a clinical trial eligibility criterion to increase the probability that patients will live long enough to experience a benefit from the treatment. Even in the clinical trial setting, however, it is falling out of favor because clinicians are poor at predicting life expectancy and because of the inability to reliably document or verify life expectancy prospectively. Retrospective ascertainment of survival duration is not appropriate for determining what a patient’s life expectancy was because survival duration is intrinsically stochastic. Yet I have learned of an example where payment was withheld from a physician when a patient died within six months of treatment, even though the cause of death was due to complications from a procedure. This clearly is not what CMS intends under its coverage decision. The NCD should state explicitly that life expectancy should not be used as a coverage criterion and coverage should not be denied retroactively because a patient dies within six months of receiving treatment.
• Metastatic disease. Physicians can readily make the diagnosis of metastatic disease and document its presence. To allow for future advances, the method by which metastatic disease is determined would best not be specified in the NCD. In addition, the NCD should clarify that there is no requirement for tissue evidence of metastasis, because such evidence is not regularly obtained in clinical practice, given that bone and lymph nodes are the typical sites of metastatic disease.
• Documentation of prostate cancer. Some MACs have been requiring histologic documentation of the diagnosis of prostate cancer before covering PROVENGE for a beneficiary. This requirement may introduce delays in treatment or lead to unnecessary procedures being performed. The vast majority of prostate cancer patients do have histologic documentation of their disease. But the tissue may have been obtained in the distant past, and documentation may not be available. Moreover, the occasional patient is diagnosed with prostate cancer based on having a markedly elevated PSA level and characteristic bone lesions, without a tissue diagnosis. I expect that it is not CMS’ intent for its coverage requirement for histologic documentation of prostate cancer to lead either to unnecessary invasive biopsies or to some patients being denied treatment even though they meet the clinical definition of prostate cancer. Instead of histologic documentation of the diagnosis of prostate cancer, the NCD should clarify that the only documentation needed should be the reporting of International Classification of Diseases, Clinical Modification (ICD-9-CM) code 185.0, malignant neoplasm of prostate.
• Immunosuppression. The FDA-approved label addresses how to assess the use of immunosuppressive agents in the context of PROVENGE. Patients enrolled in the pivotal trials were not allowed to be on immunosuppressive agents, but the FDA has translated this trial criterion into information for physicians to consider prior to starting the drug. Because of the large variety of types of these agents, as well as routes of administration and degree of immunosuppression resulting from them, it would best be left to physician judgment to determine which patients are appropriate candidates for PROVENGE. For patients with meaningful immunosuppression, we anticipate difficulty manufacturing PROVENGE (e.g., due to insufficient cells or activation of antigen presenting cells) and CMS would not be billed accordingly. But, there may be patients on low doses of immunosuppressive agents for whom a product could be readily manufactured and who would be expected to benefit from PROVENGE. Thus, the NCD should specify that coverage should not be denied solely because a beneficiary is on an agent that is causing or may cause immune suppression.
• Visceral disease. Visceral disease is not included in the FDA-approved indication statement. Attempting to use the presence of visceral disease as a coverage exclusion criterion poses several problems. First, visceral metastases are not common in men with asymptomatic or minimally symptomatic prostate cancer. Requiring physicians to rule out the presence of visceral metastases would lead to additional imaging studies which are not part of routine care. Whether or not abnormalities on imaging studies represent metastatic disease is frequently uncertain, and could lead to further work-up, including biopsies which are costly and place the patient at risk for complications. Lung nodules observed on chest x-rays are relatively common in an elderly patient population. In the clinical trials, sequential scans and measurements were used to reduce the probability that a lung abnormality represented metastatic disease, but this would be difficult to implement outside of clinical trials, and could unnecessarily lead to delays in treatment or precipitate invasive biopsies. The NCD should state that testing for the presence of visceral disease is not required prior to treatment with PROVENGE and coverage shall not be denied solely on the basis of the presence of visceral disease.
• Bisphosphonates. Some of the MACs have policies that do not cover PROVENGE for patients taking bisphosphonates. This was never a restriction in the Phase 3 trials; patients were only limited in that they could neither start nor stop bisphosphonates within 28 days of trial entry, a criterion introduced for reasons related to a secondary endpoint in the trial but unrelated to the efficacy or mechanism of action of PROVENGE. Subgroup analyses have demonstrated that patients taking bisphosphonates experience a positive PROVENGE treatment effect. The NCD should clearly state that PROVENGE is covered for beneficiaries taking bisphosphonates who otherwise meet the criteria for coverage.
• Infectious disease testing. The IMPACT trial required negative viral testing for HIV and HTLV because of requirements by certain medical centers for the testing and labeling of blood products. Dendreon no longer mandates viral testing for patients receiving PROVENGE either in clinical trials or as part of their routine care. Patients with controlled HIV/HTLV disease would be appropriate candidates for PROVENGE and should not be excluded from coverage. The NCD should state that testing for HIV and HTLV are not required prior to use of PROVENGE and coverage shall not be denied solely on the basis of HIV/HTLV disease.

In addition, I am concerned that throughout the Proposed Decision Memo, CMS does not acknowledge that PROVENGE is a biological product and repeatedly distinguishes it from other “manufactured pharmaceuticals” or “infused anti-cancer therapies.” PROVENGE was approved by CBER at FDA under a BLA. It is regulated under both the Public Health Service Act and the Food, Drug, and Cosmetic Act. Although it is covered incident to a physician service, PROVENGE meets the definition of “drugs and biologicals” under section 1861(t) of the Social Security Act. It is approved for inclusion in the United States Pharmacopoeia and is approved by the pharmacy and drug therapeutics committee of numerous hospitals across the country. The facilities used to manufacture PROVENGE were subject to full “chemistry, manufacturing, and controls” review by FDA. (2) These controls assure the finished pharmaceutical product is safe, pure, and potent, and that the product meets federal purity, identity, and quality standards. The manufacturing facilities are licensed by FDA, subject to routine FDA inspection, and must meet the full panoply of good manufacturing practice regulations designed to assure that products made in those facilities are not adulterated. Were Dendreon to change the process or the facilities in a material way, FDA review of the proposed changes would be required. This is one of the numerous reasons PROVENGE cannot be manufactured in a hospital pharmacy or clinical laboratory. Given these features of PROVENGE, I am puzzled why the Proposed Decision Memo states that PROVENGE is not “manufactured and sold by a biopharmaceutical company and then purchased by and dispensed from a pharmacy” like other anti-cancer therapies. Other than being shipped directly from the manufacturing facility to the provider, which is common for many oncology drugs, this simply is not so. CMS should correct this in its final decision memo.

* * *

In summary, I agree with your determination that PROVENGE is reasonable and necessary for patients who match the indication statement on the FDA label, and fully support the decision to give the MACs coverage discretion for off-label use, which is not currently supported by clinical evidence. However, I am concerned that the MACs are currently applying clinical trial eligibility criteria as coverage criteria, rather than the patient characteristics on the FDA label, and that this problem may be exacerbated or perpetuated by the inclusion of Appendix D. Use of clinical trial eligibility or other criteria not included in the FDA label will lead to inappropriate and inconsistent restrictions of coverage for patients who would be expected based on clinical studies to benefit from treatment. For that reason, I recommend that in the NCD you specify which criteria are and are not relevant to coverage, and have those criteria match closely with the indication statement on the FDA label. For example, as detailed above, the NCD should clearly state that a minimum PSA level or life expectancy, current evidence of disease progression, or infectious disease testing are not required for PROVENGE to be covered.

We sincerely appreciate the rigor of your evidence-based process as well as your willingness to meet with us during your consideration of this national coverage analysis. Thank you for your thoughtful consideration of these comments as well.

Sincerely,

(1) Proposed Decision Memo for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (CAG-00422N), available at: http://www.cms.gov/medicare-coverage-database/details/nca-proposed-decision-memo.aspx?NCAId=247

(2) See http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ UCM214287.pdf

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Dr. Donald Berwick
Administrator
Centers for Medicare & Medicaid Services
Mail Stop 314G?
200 Independence Ave. SW
Washington, DC 20201?
Donald.Berwick@CMS.hhs.gov

Dear Dr. Berwick,

I want to express my earnest belief and support for CMS’ draft memo which endorses full on-label coverage of the therapy known as Provenge, noting that this novel biologic is assuredly “reasonable and necessary” for men with advanced prostate cancer.

As I’ve previously written to CMS, in my work as a practicing urologist and the Medical Director for the Carolina Urologic Research Center, I have had the opportunity to participate in clinical trials of PROVENGE (sipuleucel-T) as well as having prescribed the therapy since U.S.Food and Drug Administration approval in April, 2010. Through this participation, I have seen both the individual benefit of the treatment as well as the exceptionally clear clinical evidence that PROVENGE is an efficacious and necessary option for patients fighting advanced prostate cancer. This therapy has been provided to men who are battling a lethal disease, and who will not simply succumb to “old age”. The therapy prolongs survival with minimal impact upon quality of life, and requires a very short duration of therapy, approximately 30-45 days. Unfortunately, last year prostate cancer mortalities were responsible for the lives of almost 32,000 men, thus we cannot ignore the devastating impact upon these men, their families, and their communities. We must allow these citizens access to all innovative and new treatment options, such as Provenge. Most recently, I had the honor to speak before the Congressional Black Caucus regarding the ongoing disparity of prostate cancer mortality for African Americans in the Unites States, especially profound in the southeastern states and the District of Columbia. At the CMS Medcac review on November 17, 2010, data was presented describing the potential for an even more substantial effect of Provenge for African American men with mCRPC. We must continue to substantiate this data and not limit access of Provenge to these men. Of note, the LUGPA, PHEN, and the NCBC are jointly supporting a Father’s Day rally aimed at ending this horrific disparity.

Hundreds of physicians and thousands of patients have participated in clinical trials over the last decade in the hope that PROVENGE would become available to men with advanced staged prostate cancer. I implore CMS to ensure that their final coverage decision directs that its contractors to reimburse efficiently and effectively for this breakthrough therapy so that the Medicare population and patients like mine have access to a humane and effective therapy that significantly prolongs survival. Of note, I am very fortunate that I am under the auspices of Palmetto CMS, and specifically that our carrier director is Dr. Elaine Jeter. Because of her tireless dedication to reviewing the published data as well as her understanding of the clinical unmet need which faces patients with mCRPC, my patients have been receiving Medicare coverage since Provenge approval in April 2010. Dr Jeter has always effectively communicated her review of new therapeutic advances and has been stalwart in ensuring appropriate coverage for FDA approved therapies. Please continue to allow CMS to support the FDA labeled indication for Provenge, and please do not allow for unnecessary barriers to prevent our patients from receiving this therapy In the final NCD policy, CMS should be very clear to support payment for the FDA approved indication of Provenge and ensure that men with metastatic, castrate-resistant prostate cancer have access to Provenge per its FDA-approved label.

I sincerely hope that this FDA approved therapy will also encourage more patients and physicians to participate in ongoing clinical trials which can lead to further advances in our battle against prostate cancer. Finally, I hope that by providing for true on-label access to this therapy, CMS will be supporting efforts to finally make a significant impact on the disparity in prostate cancer mortality that afflicts our African American community. Please read http://prostatehealthed.org/CBC_Support_letter.pdf.

Sincerely,

Neal D. Shore, MD, FACS
Atlantic Urology Clinics
Director, Carolina Urologic Research
Center
Myrtle Beach, SC

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*Men fighting advanced prostate cancer must have available all the tools we know that extend their life. Currently, there are only three of these tools available, one of which is Provenge. *

*There is no excuse that any man who falls within the population that the evidence has clearly demonstrated will experience life extension should not have Provenge available through Medicaid or Medicare.*

*It is clear from the Centers for Medicare and Medicaid Services (CMS) draft determination that the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment – sipuleucel-T; PROVENGE® improves health outcomes, extends life, for beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication under 1862(a)(1)(A) of the Social Security Act (the Act). *

*I urge that Provenge be fully covered under the Social Security Act and that the rules be written to be clear that any man meeting the qualifications be provided the required coverage.*

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Speaking on behalf of myself and Women Against Prostate Cancer, a national nonprofit dedicated to providing support and resources to the women who love prostate cancer patients, I strongly support CMS’ draft determination that the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment - sipuleucel-T ; PROVENGE® improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary.

As you know, in 2010 approximately 220,000 men were projected to be diagnosed with prostate cancer over 32,000 men were projected to die from the disease. Prostate cancer, particularly advanced prostate cancer, can bring many challenges to not only the patient but his entire family. Having access to a additional treatment options for patients is critical.

We would also encourage CMS to ensure that local Medicare contractors do not add any additional barriers to access for Provenge. The final national coverage determination should clear up any ambiguity between Provenge’s clinical trial enrollment criteria and the FDA approved label to ensure access to all men in need.

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Men fighting advanced prostate cancer must have available all the tools we know that extend their life. Currently, there are only three of these tools available, one of which is Provenge.

There is no excuse that any man who falls within the population that the evidence has clearly demonstrated will experience life extension should not have Provenge available through Medicaid or Medicare.

It is clear from the Centers for Medicare and Medicaid Services (CMS) draft determination that the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment – sipuleucel-T; PROVENGE® improves health outcomes, extends life, for beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication under 1862(a)(1)(A) of the Social Security Act (the Act).

I urge that Provenge be fully covered under the Social Security Act and that the rules be written to be clear that any man meeting the qualifications be provided the required coverage.

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I agree with the CMS's careful and thorough analysis which resulted in the interim determination released March 30. Autologous Cellular Immunotherapy has survival benefits which far exceed existing cancer treatments, while also offering substantial quality of life benefits due to its insignificant side effects.

Furthermore, this technology is a groundbreaking one, and as more information is learned from a larger population of users insights will likely be gleaned which will advance treatments of other types of cancer besides prostate.

I believe that the well-conceived interim determination should be promulgated as the final determination, without any changes or alterations being made thereto.

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RegenceRx conducts independent analyses of medications. Our evidence-based clinical review has concluded that the evidence supporting sipuleucel-T (Provenge) is unreliable, the impact it will have on patients is uncertain, and its treatment value is questionable.

The evidence for sipuleucel-T (Provenge) in the first-line salvage treatment of asymptomatic (or minimally symptomatic) metastatic hormone resistant prostate cancer is unreliable due to major flaws in the design and conduct of the study that include, but are not limited to:

1. Unblinding, which was allowed after disease progression was confirmed. Lack of blinding may allow for elements of bias which could overstate the effectiveness of sipuleucel-T (Provenge) on the primary outcome (of survival.)

2. Crossover to alternative therapies after disease progression was allowed at the discretion of the investigator. (This occurred in a large proportion of subjects). Follow up chemotherapy with potentially active agents such as docetaxel may confound the overall survival endpoint.

Because of these flaws, it is not known whether the overall survival benefit reported in the trial was due to sipuleucel-T (Provenge), follow up chemotherapy (docetaxel), or a combination of these two therapies. Additionally, the magnitude of this potential benefit is uncertain.

A sensitivity analysis was conducted by the FDA to determine whether subsequent docetaxel (Taxotere) use may have affected the overall survival difference observed in the trial. The FDA’s analysis suggested that it was not possible to determine whether the observed survival benefit was due to sipuleucel-T (Provenge), follow up docetaxel (Taxotere), or a combination of the two therapies.

If CMS does decide to cover sipuleucel-T (Provenge), RegenceRx recommends the following coverage criteria:

• Asymptomatic or minimally symptomatic metastatic, hormone resistant prostate cancer (minimally symptomatic as evidenced by no narcotic (opioid) use for prostate cancer-related pain.); and
• ECOG (Eastern Cooperative Oncology Group) performance status 0-1; and
• No visceral metastasis, pathologic long bone fracture, or spinal cord compression; and
• Life expectancy of greater than 6 months; and
• Serum prostate-specific antigen (PSA) level of 5 ng/ml or more; and
• Serum testosterone level less than 50 ng/dl (17 nmol/l); and
• Progressive disease based on imaging studies or PSA measurements; and
• No treatment within the previous 28 days with systemic glucocorticoids, external-beam radiation (EBRT), surgery, or systemic therapy for prostate cancer (except medical or surgical castration); and
• No chemotherapy within the previous 6 months.

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Thanks to CMS for its well-considered draft opinion regarding provenge. I believe that health care is one area in which additional jobs are being created. The development of advances in medicine is a critical element of this job creation. It is also an important aspect of world leadership by the United States in scientific matters. The dawn of the age of cancer immunotherapies holds great promise for the fight against this dreadful disease. I hope that the CMS final decision will mirror the draft decision, and that cancer immunotherapies will continue to be developed. Thank you.

Bob Ghazey

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Men fighting advanced prostate cancer must have available all the tools we know that extend their life. Currently, there are only three of these tools available, one of which is Provenge.

There is no excuse that any man who falls within the population that the evidence has clearly demonstrated will experience life extension should not have Provenge available through Medicaid or Medicare.

It is clear from the Centers for Medicare and Medicaid Services (CMS) draft determination that the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment – sipuleucel-T; PROVENGE improves health outcomes, extends life, for beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication under 1862(a)(1)(A) of the Social Security Act (the Act).

I urge that Provenge be fully covered under the Social Security Act and that the rules be written to be clear that any man meeting the qualifications be provided the required coverage.

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This is just to add an additional comment to my previous observation. I’ve lived almost 78 years and experienced unfathomable times and amazing progress enjoyed by large segments of humanity. From this perspective, one can sometimes become a somewhat detached observer of the world around as it unfolds from day to day. As I step back and study the issues before CMS with respect to the Provenge matter, I try to evaluate and understand the positions of the several respondents who have submitted written comments in opposition to using Medicare and Medicaid resources to fund the FDA approved treatment of eligible men suffering from asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer using Sipuleucel-T (Provenge). There seems to be in the opposing group a prevailing notion that it is a waste of limited resources to treat old men who probably are not going to live much longer anyway.

These opponents need to understand that PC can inflict young as well as old men. Some of us old men continue pretty active life styles. I personally have just completed my 7th marathon, am training to compete in the National Senior Games basketball tournament in June, and am assisting with the start up of a new business venture. There are many others much older and more active than I am. Two members of my senior basketball team have PC. Provenge needs to be available for them should it be required. Further, fantastic medical advancement will follow the trail blazed by Provenge to provide life saving and quality of life improving treatments for many different forms of cancer. And as we improve our medical capabilities in the United States, these advances can be made available to other nations and underserved populations all over the world. You have to start somewhere and then have good men and women doing the right thing to maximize benefits to mankind. Your proposed decision of March 30 regarding Provenge is such a start.

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Men fighting advanced prostate cancer must have available all the tools we know that extend their life. Currently, there are only three of these tools available, one of which is Provenge.

There is no excuse that any man who falls within the population that the evidence has clearly demonstrated will experience life extension should not have Provenge available through Medicaid or Medicare.

It is clear from the Centers for Medicare and Medicaid Services (CMS) draft determination that the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment – sipuleucel-T; PROVENGE® improves health outcomes, extends life, for beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication under 1862(a)(1)(A) of the Social Security Act (the Act).

I urge that Provenge be fully covered under the Social Security Act and that the rules be written to be clear that any man meeting the qualifications be provided the required coverage.

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Men fighting advanced prostate cancer must have available all the tools we know that extend their life. Currently, there are only three of these tools available, one of which is Provenge.

There is no excuse that any man who falls within the population that the evidence has clearly demonstrated will experience life extension should not have Provenge available through Medicaid or Medicare.

It is clear from the Centers for Medicare and Medicaid Services (CMS) draft determination that the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment – sipuleucel-T; PROVENGE® improves health outcomes, extends life, for beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication under 1862(a)(1)(A) of the Social Security Act (the Act).

I urge that Provenge be fully covered under the Social Security Act and that the rules be written to be clear that any man meeting the qualifications be provided the required coverage.

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Men fighting advanced prostate cancer must have available all the tools we know that extend their life. Currently, there are only three of these tools available, one of which is Provenge.

There is no excuse that any man who falls within the population that will experience life extension should not have Provenge available through Medicaid or Medicare.

It is clear from the Centers for Medicare and Medicaid Services (CMS) draft determination that the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® improves health outcomes, extends life, for beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication under 1862(a)(1)(A) of the Social Security Act (the Act).

I urge that Provenge be fully covered under the Social Security Act and that the rules be written to be clear that any man meeting the qualifications be provided the required coverage.

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April 22, 2011

Louis Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
Mail Stop S3-02-01
7500 Security Blvd.
Baltimore, MD 21244

Re: Proposed Decision Memo for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (CAG-00422N)

Dear Dr. Jacques,

As physicians who treat patients with advanced prostate cancer, we were pleased to read the Center for Medicare and Medicaid Services’ (CMS) proposed decision memorandum for sipuleucel-T (Provenge), which stated that “the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication.”

We also concur that there are no mature clinical data supporting off-label uses at this time, and that giving the administrative contractors the flexibility to adjust coverage for non-label indications, without the need to reconsider the National Coverage Determination (NCD), should additional clinical data become available, is important to allow patients to benefit from future advances in a timely manner. We do remain concerned that the broad coverage language which mirrors the FDA indication statement is not sufficiently detailed to allow providers enough guidance and structure on its use. To that end, we have carefully reviewed the FDA indication statement, as well as the clinical trial criteria for the Phase III pivotal IMPACT trial, and suggest that the following four coverage criteria be considered. These criteria could be objectively implemented.

• Diagnosis of Prostate Cancer. The diagnosis of prostate cancer is readily determined by physicians and documented by the International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) code for malignant neoplasm of the prostate. The diagnosis therefore should not require further specification. While a histologic diagnosis is frequently obtained at the time of initial diagnosis, it should not be required, as it may be difficult to obtain at the time of metastatic disease, which often occurs many years following the initial diagnosis and when care may be in the hands of a physician who did not make the initial diagnosis. Furthermore, the occasional patient may be diagnosed with metastatic prostate cancer based on a highly elevated prostate specific antigen (PSA) level in the peripheral blood in combination with a characteristic evidence of metastases on imaging studies. This is widely accepted as consistent with the diagnosis. For both of these reasons, a requirement for a histologic diagnosis could lead to unnecessary biopsy procedures or the exclusion of appropriate patients. Since many patients with metastatic disease no longer have their prostate in place, a tissue diagnosis might require biopsy of a metastatic site, typically retroperitoneal lymph nodes or bone, which is invasive and associated with some risk to the patient.
• Evidence of metastatic disease. The presence of metastatic disease is readily ascertained and documented by physicians. Specification of the modality by which metastatic disease is determined should not be necessary and would not allow for technological advances in the detection of metastatic disease.
• Castration resistant disease, as determined by current or historical evidence of disease progression in the setting of medical or surgical castration. Once a patient’s cancer becomes castration resistant, it remains castration resistant. Therefore, the diagnosis of castration resistance need not be made more than once for a particular patient. Historical evidence of castration resistance should be sufficient for coverage, just as it is sufficient for decision making in routine clinical practice. Furthermore, we urge caution regarding the extent to which the specific technologies used to determine disease progression are specified in the coverage rules, as biomarker and imaging assays for disease activity continue to evolve.
• Either asymptomatic or mildly symptomatic prostate cancer defined as not currently taking narcotics for cancer related pain. Most men diagnosed with castration resistant prostate cancer are initially quite functional and typically do not have more than minimal pain due to their disease. Limiting coverage for sipuleucel-T to men who are not receiving narcotics for cancer related pain would be the most logical and practical approach and would be consistent with our clinical use of sipuleucel-T. Likewise, by specifying non-coverage only for those patients who take narcotics for cancer-related pain, the coverage would match the description of the study entry criteria on the FDA label for sipuleucel-T and ensure that men taking narcotics for other reasons could still receive treatment with sipuleucel-T.

Specification of these four objective coverage criteria in the NCD should be sufficiently precise to give physicians guidance without creating undue burden and ensure that Medicare beneficiaries have appropriate access to sipuleucel-T. The language of the NCD should clarify that additional coverage criteria for the on-label use of this biological product, including applying the large number of technical eligibility criteria for the sipuleucel-T pivotal trial, should not be used. We would recommend removal of Appendix D with the eligibility criteria for the IMPACT trial; these criteria are available on the New England Journal of Medicine website along with the primary publication. This is important, as we have learned of several instances where clinical trial eligibility criteria, rather than the indication statement, have been applied in a manner that has led to delays or potential denial of coverage for patients who met the criteria on the FDA label. Because of the uncertainty surrounding the precise criteria which must be met for reimbursement, many men who meet the FDA label indication and could benefit from sipuleucel-T are likely not being offered it.

In summary, sipuleucel-T is an important new biological product for men with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer. We would encourage you to specify the four objective coverage criteria noted above, and to clarify that additional criteria, such as the eligibility criteria for the clinical trials of sipuleucel-T should not be used. This approach would provide clear guidance for the administrative contractors on how to implement coverage for the label indication while minimizing undue burden on physicians. Most important, it also would help ensure that coverage is uniform across the country for men with metastatic prostate cancer, and that everywhere men who meet the indication statement can have the chance to benefit from this important new biologic treatment advance. Thank you for your thoughtful consideration of our comments and for your rigorous evidence-based approach to this National Coverage Analysis.

Sincerely,

Celestia S. Higano, MD
Professor of Medicine, Medical Oncology Division
University of Washington School of Medicine

Philip W. Kantoff, MD
Professor of Medicine Harvard Medical School
Chief, Division of Solid Tumor Oncology
Director, Lank Center for Genitourinary Oncology
Department of Medical Oncology Dana-Farber Cancer Institute, Harvard Med. School

Daniel P. Petrylak, MD
Professor of Medicine
New York-Presbyterian Hospital
Columbia University Medical Center

Paul F. Schellhammer, MD, FACS
Professor of Urology
Eastern Virginia Medical School

Eric J. Small, MD
Professor of Medicine and Urology
Norman and Stanford Ascherman Endowed Chair
Chief, Division of Hematology and Oncology
Director of Clinical Sciences
Deputy Director, UCSF Helen Diller Family Comprehensive Cancer Center

Less

April 22, 2011

Louis Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
Mail Stop S3-02-01
7500 Security Blvd.
Baltimore, MD 21244

Re: Proposed Decision Memo for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (CAG-00422N)

Dear Dr. Jacques,

As physicians who treat patients with advanced prostate cancer, we were pleased to read the Center for Medicare and Medicaid Services’ (CMS) proposed decision memorandum for sipuleucel-T (Provenge), which stated that “the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication.”

We also concur that there are no mature clinical data supporting off-label uses at this time, and that giving the administrative contractors the flexibility to adjust coverage for non-label indications, without the need to reconsider the National Coverage Determination (NCD), should additional clinical data become available, is important to allow patients to benefit from future advances in a timely manner. We do remain concerned that the broad coverage language which mirrors the FDA indication statement is not sufficiently detailed to allow providers enough guidance and structure on its use. To that end, we have carefully reviewed the FDA indication statement, as well as the clinical trial criteria for the Phase III pivotal IMPACT trial, and suggest that the following four coverage criteria be considered. These criteria could be objectively implemented.

• Diagnosis of Prostate Cancer. The diagnosis of prostate cancer is readily determined by physicians and documented by the International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) code for malignant neoplasm of the prostate. The diagnosis therefore should not require further specification. While a histologic diagnosis is frequently obtained at the time of initial diagnosis, it should not be required, as it may be difficult to obtain at the time of metastatic disease, which often occurs many years following the initial diagnosis and when care may be in the hands of a physician who did not make the initial diagnosis. Furthermore, the occasional patient may be diagnosed with metastatic prostate cancer based on a highly elevated prostate specific antigen (PSA) level in the peripheral blood in combination with a characteristic evidence of metastases on imaging studies. This is widely accepted as consistent with the diagnosis. For both of these reasons, a requirement for a histologic diagnosis could lead to unnecessary biopsy procedures or the exclusion of appropriate patients. Since many patients with metastatic disease no longer have their prostate in place, a tissue diagnosis might require biopsy of a metastatic site, typically retroperitoneal lymph nodes or bone, which is invasive and associated with some risk to the patient.
• Evidence of metastatic disease. The presence of metastatic disease is readily ascertained and documented by physicians. Specification of the modality by which metastatic disease is determined should not be necessary and would not allow for technological advances in the detection of metastatic disease.
• Castration resistant disease, as determined by current or historical evidence of disease progression in the setting of medical or surgical castration. Once a patient’s cancer becomes castration resistant, it remains castration resistant. Therefore, the diagnosis of castration resistance need not be made more than once for a particular patient. Historical evidence of castration resistance should be sufficient for coverage, just as it is sufficient for decision making in routine clinical practice. Furthermore, we urge caution regarding the extent to which the specific technologies used to determine disease progression are specified in the coverage rules, as biomarker and imaging assays for disease activity continue to evolve.
• Either asymptomatic or mildly symptomatic prostate cancer defined as not currently taking narcotics for cancer related pain. Most men diagnosed with castration resistant prostate cancer are initially quite functional and typically do not have more than minimal pain due to their disease. Limiting coverage for sipuleucel-T to men who are not receiving narcotics for cancer related pain would be the most logical and practical approach and would be consistent with our clinical use of sipuleucel-T. Likewise, by specifying non-coverage only for those patients who take narcotics for cancer-related pain, the coverage would match the description of the study entry criteria on the FDA label for sipuleucel-T and ensure that men taking narcotics for other reasons could still receive treatment with sipuleucel-T.

Specification of these four objective coverage criteria in the NCD should be sufficiently precise to give physicians guidance without creating undue burden and ensure that Medicare beneficiaries have appropriate access to sipuleucel-T. The language of the NCD should clarify that additional coverage criteria for the on-label use of this biological product, including applying the large number of technical eligibility criteria for the sipuleucel-T pivotal trial, should not be used. We would recommend removal of Appendix D with the eligibility criteria for the IMPACT trial; these criteria are available on the New England Journal of Medicine website along with the primary publication. This is important, as we have learned of several instances where clinical trial eligibility criteria, rather than the indication statement, have been applied in a manner that has led to delays or potential denial of coverage for patients who met the criteria on the FDA label. Because of the uncertainty surrounding the precise criteria which must be met for reimbursement, many men who meet the FDA label indication and could benefit from sipuleucel-T are likely not being offered it.

In summary, sipuleucel-T is an important new biological product for men with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer. We would encourage you to specify the four objective coverage criteria noted above, and to clarify that additional criteria, such as the eligibility criteria for the clinical trials of sipuleucel-T should not be used. This approach would provide clear guidance for the administrative contractors on how to implement coverage for the label indication while minimizing undue burden on physicians. Most important, it also would help ensure that coverage is uniform across the country for men with metastatic prostate cancer, and that everywhere men who meet the indication statement can have the chance to benefit from this important new biologic treatment advance. Thank you for your thoughtful consideration of our comments and for your rigorous evidence-based approach to this National Coverage Analysis.

Sincerely,

Celestia S. Higano, MD
Professor of Medicine, Medical Oncology Division
University of Washington School of Medicine

Philip W. Kantoff, MD
Professor of Medicine Harvard Medical School
Chief, Division of Solid Tumor Oncology
Director, Lank Center for Genitourinary Oncology
Department of Medical Oncology Dana-Farber Cancer Institute, Harvard Med. School

Daniel P. Petrylak, MD
Professor of Medicine
New York-Presbyterian Hospital
Columbia University Medical Center

Paul F. Schellhammer, MD, FACS
Professor of Urology
Eastern Virginia Medical School

Eric J. Small, MD
Professor of Medicine and Urology
Norman and Stanford Ascherman Endowed Chair
Chief, Division of Hematology and Oncology
Director of Clinical Sciences
Deputy Director, UCSF Helen Diller Family Comprehensive Cancer Center

Less

April 22, 2011

Louis Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
Mail Stop S3-02-01
7500 Security Blvd.
Baltimore, MD 21244

Re: Proposed Decision Memo for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (CAG-00422N)

Dear Dr. Jacques,

As physicians who treat patients with advanced prostate cancer, we were pleased to read the Center for Medicare and Medicaid Services’ (CMS) proposed decision memorandum for sipuleucel-T (Provenge), which stated that “the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication.”

We also concur that there are no mature clinical data supporting off-label uses at this time, and that giving the administrative contractors the flexibility to adjust coverage for non-label indications, without the need to reconsider the National Coverage Determination (NCD), should additional clinical data become available, is important to allow patients to benefit from future advances in a timely manner. We do remain concerned that the broad coverage language which mirrors the FDA indication statement is not sufficiently detailed to allow providers enough guidance and structure on its use. To that end, we have carefully reviewed the FDA indication statement, as well as the clinical trial criteria for the Phase III pivotal IMPACT trial, and suggest that the following four coverage criteria be considered. These criteria could be objectively implemented.

• Diagnosis of Prostate Cancer. The diagnosis of prostate cancer is readily determined by physicians and documented by the International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) code for malignant neoplasm of the prostate. The diagnosis therefore should not require further specification. While a histologic diagnosis is frequently obtained at the time of initial diagnosis, it should not be required, as it may be difficult to obtain at the time of metastatic disease, which often occurs many years following the initial diagnosis and when care may be in the hands of a physician who did not make the initial diagnosis. Furthermore, the occasional patient may be diagnosed with metastatic prostate cancer based on a highly elevated prostate specific antigen (PSA) level in the peripheral blood in combination with a characteristic evidence of metastases on imaging studies. This is widely accepted as consistent with the diagnosis. For both of these reasons, a requirement for a histologic diagnosis could lead to unnecessary biopsy procedures or the exclusion of appropriate patients. Since many patients with metastatic disease no longer have their prostate in place, a tissue diagnosis might require biopsy of a metastatic site, typically retroperitoneal lymph nodes or bone, which is invasive and associated with some risk to the patient.
• Evidence of metastatic disease. The presence of metastatic disease is readily ascertained and documented by physicians. Specification of the modality by which metastatic disease is determined should not be necessary and would not allow for technological advances in the detection of metastatic disease.
• Castration resistant disease, as determined by current or historical evidence of disease progression in the setting of medical or surgical castration. Once a patient’s cancer becomes castration resistant, it remains castration resistant. Therefore, the diagnosis of castration resistance need not be made more than once for a particular patient. Historical evidence of castration resistance should be sufficient for coverage, just as it is sufficient for decision making in routine clinical practice. Furthermore, we urge caution regarding the extent to which the specific technologies used to determine disease progression are specified in the coverage rules, as biomarker and imaging assays for disease activity continue to evolve.
• Either asymptomatic or mildly symptomatic prostate cancer defined as not currently taking narcotics for cancer related pain. Most men diagnosed with castration resistant prostate cancer are initially quite functional and typically do not have more than minimal pain due to their disease. Limiting coverage for sipuleucel-T to men who are not receiving narcotics for cancer related pain would be the most logical and practical approach and would be consistent with our clinical use of sipuleucel-T. Likewise, by specifying non-coverage only for those patients who take narcotics for cancer-related pain, the coverage would match the description of the study entry criteria on the FDA label for sipuleucel-T and ensure that men taking narcotics for other reasons could still receive treatment with sipuleucel-T.

Specification of these four objective coverage criteria in the NCD should be sufficiently precise to give physicians guidance without creating undue burden and ensure that Medicare beneficiaries have appropriate access to sipuleucel-T. The language of the NCD should clarify that additional coverage criteria for the on-label use of this biological product, including applying the large number of technical eligibility criteria for the sipuleucel-T pivotal trial, should not be used. We would recommend removal of Appendix D with the eligibility criteria for the IMPACT trial; these criteria are available on the New England Journal of Medicine website along with the primary publication. This is important, as we have learned of several instances where clinical trial eligibility criteria, rather than the indication statement, have been applied in a manner that has led to delays or potential denial of coverage for patients who met the criteria on the FDA label. Because of the uncertainty surrounding the precise criteria which must be met for reimbursement, many men who meet the FDA label indication and could benefit from sipuleucel-T are likely not being offered it.

In summary, sipuleucel-T is an important new biological product for men with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer. We would encourage you to specify the four objective coverage criteria noted above, and to clarify that additional criteria, such as the eligibility criteria for the clinical trials of sipuleucel-T should not be used. This approach would provide clear guidance for the administrative contractors on how to implement coverage for the label indication while minimizing undue burden on physicians. Most important, it also would help ensure that coverage is uniform across the country for men with metastatic prostate cancer, and that everywhere men who meet the indication statement can have the chance to benefit from this important new biologic treatment advance. Thank you for your thoughtful consideration of our comments and for your rigorous evidence-based approach to this National Coverage Analysis.

Sincerely,

Celestia S. Higano, MD
Professor of Medicine, Medical Oncology Division
University of Washington School of Medicine

Philip W. Kantoff, MD
Professor of Medicine Harvard Medical School
Chief, Division of Solid Tumor Oncology
Director, Lank Center for Genitourinary Oncology
Department of Medical Oncology Dana-Farber Cancer Institute, Harvard Med. School

Daniel P. Petrylak, MD
Professor of Medicine
New York-Presbyterian Hospital
Columbia University Medical Center

Paul F. Schellhammer, MD, FACS
Professor of Urology
Eastern Virginia Medical School

Eric J. Small, MD
Professor of Medicine and Urology
Norman and Stanford Ascherman Endowed Chair
Chief, Division of Hematology and Oncology
Director of Clinical Sciences
Deputy Director, UCSF Helen Diller Family Comprehensive Cancer Center

Less

April 22, 2011

Louis Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
Mail Stop S3-02-01
7500 Security Blvd.
Baltimore, MD 21244

Re: Proposed Decision Memo for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (CAG-00422N)

Dear Dr. Jacques,

As physicians who treat patients with advanced prostate cancer, we were pleased to read the Center for Medicare and Medicaid Services’ (CMS) proposed decision memorandum for sipuleucel-T (Provenge), which stated that “the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication.”

We also concur that there are no mature clinical data supporting off-label uses at this time, and that giving the administrative contractors the flexibility to adjust coverage for non-label indications, without the need to reconsider the National Coverage Determination (NCD), should additional clinical data become available, is important to allow patients to benefit from future advances in a timely manner. We do remain concerned that the broad coverage language which mirrors the FDA indication statement is not sufficiently detailed to allow providers enough guidance and structure on its use. To that end, we have carefully reviewed the FDA indication statement, as well as the clinical trial criteria for the Phase III pivotal IMPACT trial, and suggest that the following four coverage criteria be considered. These criteria could be objectively implemented.

• Diagnosis of Prostate Cancer. The diagnosis of prostate cancer is readily determined by physicians and documented by the International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) code for malignant neoplasm of the prostate. The diagnosis therefore should not require further specification. While a histologic diagnosis is frequently obtained at the time of initial diagnosis, it should not be required, as it may be difficult to obtain at the time of metastatic disease, which often occurs many years following the initial diagnosis and when care may be in the hands of a physician who did not make the initial diagnosis. Furthermore, the occasional patient may be diagnosed with metastatic prostate cancer based on a highly elevated prostate specific antigen (PSA) level in the peripheral blood in combination with a characteristic evidence of metastases on imaging studies. This is widely accepted as consistent with the diagnosis. For both of these reasons, a requirement for a histologic diagnosis could lead to unnecessary biopsy procedures or the exclusion of appropriate patients. Since many patients with metastatic disease no longer have their prostate in place, a tissue diagnosis might require biopsy of a metastatic site, typically retroperitoneal lymph nodes or bone, which is invasive and associated with some risk to the patient.
• Evidence of metastatic disease. The presence of metastatic disease is readily ascertained and documented by physicians. Specification of the modality by which metastatic disease is determined should not be necessary and would not allow for technological advances in the detection of metastatic disease.
• Castration resistant disease, as determined by current or historical evidence of disease progression in the setting of medical or surgical castration. Once a patient’s cancer becomes castration resistant, it remains castration resistant. Therefore, the diagnosis of castration resistance need not be made more than once for a particular patient. Historical evidence of castration resistance should be sufficient for coverage, just as it is sufficient for decision making in routine clinical practice. Furthermore, we urge caution regarding the extent to which the specific technologies used to determine disease progression are specified in the coverage rules, as biomarker and imaging assays for disease activity continue to evolve.
• Either asymptomatic or mildly symptomatic prostate cancer defined as not currently taking narcotics for cancer related pain. Most men diagnosed with castration resistant prostate cancer are initially quite functional and typically do not have more than minimal pain due to their disease. Limiting coverage for sipuleucel-T to men who are not receiving narcotics for cancer related pain would be the most logical and practical approach and would be consistent with our clinical use of sipuleucel-T. Likewise, by specifying non-coverage only for those patients who take narcotics for cancer-related pain, the coverage would match the description of the study entry criteria on the FDA label for sipuleucel-T and ensure that men taking narcotics for other reasons could still receive treatment with sipuleucel-T.

Specification of these four objective coverage criteria in the NCD should be sufficiently precise to give physicians guidance without creating undue burden and ensure that Medicare beneficiaries have appropriate access to sipuleucel-T. The language of the NCD should clarify that additional coverage criteria for the on-label use of this biological product, including applying the large number of technical eligibility criteria for the sipuleucel-T pivotal trial, should not be used. We would recommend removal of Appendix D with the eligibility criteria for the IMPACT trial; these criteria are available on the New England Journal of Medicine website along with the primary publication. This is important, as we have learned of several instances where clinical trial eligibility criteria, rather than the indication statement, have been applied in a manner that has led to delays or potential denial of coverage for patients who met the criteria on the FDA label. Because of the uncertainty surrounding the precise criteria which must be met for reimbursement, many men who meet the FDA label indication and could benefit from sipuleucel-T are likely not being offered it.

In summary, sipuleucel-T is an important new biological product for men with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer. We would encourage you to specify the four objective coverage criteria noted above, and to clarify that additional criteria, such as the eligibility criteria for the clinical trials of sipuleucel-T should not be used. This approach would provide clear guidance for the administrative contractors on how to implement coverage for the label indication while minimizing undue burden on physicians. Most important, it also would help ensure that coverage is uniform across the country for men with metastatic prostate cancer, and that everywhere men who meet the indication statement can have the chance to benefit from this important new biologic treatment advance. Thank you for your thoughtful consideration of our comments and for your rigorous evidence-based approach to this National Coverage Analysis.

Sincerely,

Celestia S. Higano, MD
Professor of Medicine, Medical Oncology Division
University of Washington School of Medicine

Philip W. Kantoff, MD
Professor of Medicine Harvard Medical School
Chief, Division of Solid Tumor Oncology
Director, Lank Center for Genitourinary Oncology
Department of Medical Oncology Dana-Farber Cancer Institute, Harvard Med. School

Daniel P. Petrylak, MD
Professor of Medicine
New York-Presbyterian Hospital
Columbia University Medical Center

Paul F. Schellhammer, MD, FACS
Professor of Urology
Eastern Virginia Medical School

Eric J. Small, MD
Professor of Medicine and Urology
Norman and Stanford Ascherman Endowed Chair
Chief, Division of Hematology and Oncology
Director of Clinical Sciences
Deputy Director, UCSF Helen Diller Family Comprehensive Cancer Center

Less

April 22, 2011

Louis Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
Mail Stop S3-02-01
7500 Security Blvd.
Baltimore, MD 21244

Re: Proposed Decision Memo for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (CAG-00422N)

Dear Dr. Jacques,

As physicians who treat patients with advanced prostate cancer, we were pleased to read the Center for Medicare and Medicaid Services’ (CMS) proposed decision memorandum for sipuleucel-T (Provenge), which stated that “the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication.”

We also concur that there are no mature clinical data supporting off-label uses at this time, and that giving the administrative contractors the flexibility to adjust coverage for non-label indications, without the need to reconsider the National Coverage Determination (NCD), should additional clinical data become available, is important to allow patients to benefit from future advances in a timely manner. We do remain concerned that the broad coverage language which mirrors the FDA indication statement is not sufficiently detailed to allow providers enough guidance and structure on its use. To that end, we have carefully reviewed the FDA indication statement, as well as the clinical trial criteria for the Phase III pivotal IMPACT trial, and suggest that the following four coverage criteria be considered. These criteria could be objectively implemented.

• Diagnosis of Prostate Cancer. The diagnosis of prostate cancer is readily determined by physicians and documented by the International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) code for malignant neoplasm of the prostate. The diagnosis therefore should not require further specification. While a histologic diagnosis is frequently obtained at the time of initial diagnosis, it should not be required, as it may be difficult to obtain at the time of metastatic disease, which often occurs many years following the initial diagnosis and when care may be in the hands of a physician who did not make the initial diagnosis. Furthermore, the occasional patient may be diagnosed with metastatic prostate cancer based on a highly elevated prostate specific antigen (PSA) level in the peripheral blood in combination with a characteristic evidence of metastases on imaging studies. This is widely accepted as consistent with the diagnosis. For both of these reasons, a requirement for a histologic diagnosis could lead to unnecessary biopsy procedures or the exclusion of appropriate patients. Since many patients with metastatic disease no longer have their prostate in place, a tissue diagnosis might require biopsy of a metastatic site, typically retroperitoneal lymph nodes or bone, which is invasive and associated with some risk to the patient.
• Evidence of metastatic disease. The presence of metastatic disease is readily ascertained and documented by physicians. Specification of the modality by which metastatic disease is determined should not be necessary and would not allow for technological advances in the detection of metastatic disease.
• Castration resistant disease, as determined by current or historical evidence of disease progression in the setting of medical or surgical castration. Once a patient’s cancer becomes castration resistant, it remains castration resistant. Therefore, the diagnosis of castration resistance need not be made more than once for a particular patient. Historical evidence of castration resistance should be sufficient for coverage, just as it is sufficient for decision making in routine clinical practice. Furthermore, we urge caution regarding the extent to which the specific technologies used to determine disease progression are specified in the coverage rules, as biomarker and imaging assays for disease activity continue to evolve.
• Either asymptomatic or mildly symptomatic prostate cancer defined as not currently taking narcotics for cancer related pain. Most men diagnosed with castration resistant prostate cancer are initially quite functional and typically do not have more than minimal pain due to their disease. Limiting coverage for sipuleucel-T to men who are not receiving narcotics for cancer related pain would be the most logical and practical approach and would be consistent with our clinical use of sipuleucel-T. Likewise, by specifying non-coverage only for those patients who take narcotics for cancer-related pain, the coverage would match the description of the study entry criteria on the FDA label for sipuleucel-T and ensure that men taking narcotics for other reasons could still receive treatment with sipuleucel-T.

Specification of these four objective coverage criteria in the NCD should be sufficiently precise to give physicians guidance without creating undue burden and ensure that Medicare beneficiaries have appropriate access to sipuleucel-T. The language of the NCD should clarify that additional coverage criteria for the on-label use of this biological product, including applying the large number of technical eligibility criteria for the sipuleucel-T pivotal trial, should not be used. We would recommend removal of Appendix D with the eligibility criteria for the IMPACT trial; these criteria are available on the New England Journal of Medicine website along with the primary publication. This is important, as we have learned of several instances where clinical trial eligibility criteria, rather than the indication statement, have been applied in a manner that has led to delays or potential denial of coverage for patients who met the criteria on the FDA label. Because of the uncertainty surrounding the precise criteria which must be met for reimbursement, many men who meet the FDA label indication and could benefit from sipuleucel-T are likely not being offered it.

In summary, sipuleucel-T is an important new biological product for men with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer. We would encourage you to specify the four objective coverage criteria noted above, and to clarify that additional criteria, such as the eligibility criteria for the clinical trials of sipuleucel-T should not be used. This approach would provide clear guidance for the administrative contractors on how to implement coverage for the label indication while minimizing undue burden on physicians. Most important, it also would help ensure that coverage is uniform across the country for men with metastatic prostate cancer, and that everywhere men who meet the indication statement can have the chance to benefit from this important new biologic treatment advance. Thank you for your thoughtful consideration of our comments and for your rigorous evidence-based approach to this National Coverage Analysis.

Sincerely,

Celestia S. Higano, MD
Professor of Medicine, Medical Oncology Division
University of Washington School of Medicine

Philip W. Kantoff, MD
Professor of Medicine Harvard Medical School
Chief, Division of Solid Tumor Oncology
Director, Lank Center for Genitourinary Oncology
Department of Medical Oncology Dana-Farber Cancer Institute, Harvard Med. School

Daniel P. Petrylak, MD
Professor of Medicine
New York-Presbyterian Hospital
Columbia University Medical Center

Paul F. Schellhammer, MD, FACS
Professor of Urology
Eastern Virginia Medical School

Eric J. Small, MD
Professor of Medicine and Urology
Norman and Stanford Ascherman Endowed Chair
Chief, Division of Hematology and Oncology
Director of Clinical Sciences
Deputy Director, UCSF Helen Diller Family Comprehensive Cancer Center

Less

I fully support the CMS's decision to have Medicare reimburse Provenge for FDA on-label indications and want to thank the men and women at CMS who put the time and effort to carefully come to this decision. I hope that the CMS will also consider reimbursement of Provenge for off-label indications as well.

I wanted to reiterate my original comment that Provenge is positive in terms of economics and for the benefit of humanity as a whole. Economically, the use of Provenge will over time reduce the economic burden that traditional chemotherapies cause on our health system due to their nasty side effects. Provenge is a revolutionary treatment that provides an immediate impact on those with Prostate cancer (as seen in the trial data where it was seen that Provenge provided the longest life extender ever for prostate cancer, 40% improvement in 3 year survival) and in the long run may one day lead to a cure for cancer.

Again, I want thank all those involved inside the CMS on their hard work for approving Provenge for Medicare reimbursement and fully support the draft decision.

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I am writing in support of CMS coverage of Provenge, as this autologous cellular therapy has been one of the major breakthroughs in the treatment of prostate cancer. We are enthusiastic about the FDA approval of this drug and fully support the presence of Dendreon’s state-of-the-art manufacturing facility in Metro Atlanta.

We value the efforts and success of Dendreon and therefore believe it is imperative that CMS cover this therapy to the FDA label indication to prevent barriers to patient access for the much needed treat option.

David Hartnett
Vice President, Bioscience Industry
Economic Development Division

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Dendreon received FDA approval for Provenge which proved the efficacy of ?the treatment and which were INDISPUTABLE. Dying men have patiently waited for this ?treatment to be made available. Many are no ?longer alive today as a result of past delays in ?getting Provenge to market.??Moreover from a cost perspective there is again ?misleading information. The $93k is NOT an ?annual cost. It is a one time cost for the ?treatment and most CERTAINLY compares favorably ?to the chemo options AND the costs of the ?associated drugs NECESSARY to counter the ?debilating side effects of taking the chemo path.

Joseph Man

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This ground breaking treatment needs to be available to all qualified prostate cancer patients and be approved for full reimbursement.Remember that one day you or someone in your family may have prostate cancer diagnosis and trust me when I say the alternative poison chemotherapy is worse to tolerate than the cancer itself.Provenge has virtually NO adverse side effects and when you consider the price remember chemotherapy requires significant and expensive follow up therapies just to manage the severe side effects it causes.

Please fully approve reimbursement for Provenge therapy.

Sincerely,

David

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First, thank you for your diligent work which led to the decision of tentative approval of Provenge which is extending lives right now due to your hard work and solid judgement.

I fully and whole-heartedly support the full approval of Provenge.

There are detractors who speak against Provenge on the grounds of money - although chemo and treatment related to it's side effects combine to cost taxpayers more with inferior results - but as we all know, the patients are people and are our fellow Americans, and these these Americans deserve to live as full a life as is possible and we all deserve the option of a treatment that provides the longest life extension ever for prostate cancer - Provenge.

How can anyone argue against Provenge when the "all in" costs are less than chemo, it improves quality of life and recent data shows 40% improvement in 3 year survival? One cannot ignore the facts. This is a fantastic breakthrough treatment that works and will likely save the government money while making it possible for prostate cancer patients - many of them grandparents - to see their grandchildren grow and continue to add the richness of their life experiences to our country and our communities. Please approve Provenge once and for all. Please elect to save more lives. It's the right thing to do. I say this as a parent, a friend of someone with prostate cancer and as a fellow American.

Thank you for your efforts and your kind consideration of my comments.

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On behalf of Men’s Health Network (MHN), we commend CMS for following the science around Provenge as well as providing for broad on-label access in the Proposed Decision Memo. CMS needs to be clear that this decision supports coverage according to the FDA label and that local Medicare contractors should not be adding unnecessary barriers for men who desperately need this therapy. The final National Coverage Determination should make certain that men with metastatic, castrate-resistant prostate cancer have access to Provenge per its FDA-approved label.

Prostate cancer is the most prevalent form of cancer among American males. Nearly 220,000 men were projected to be diagnosed with prostate cancer in 2010, and about 32,000 were projected to die from this disease. Men with advanced prostate cancer face many serious challenges. For these men access to treatment is of utmost importance to extend and improve their lives.

For over a decade there has been an immense need for innovative treatments to improve the plight of men suffering from advanced prostate cancer. As you know, prostate cancer is a complex and problematic disease that affects not only the male patient, but also his wife, daughter, partner, and other family members.

African-American men have one of the highest rates of incidence and death from prostate cancer in the world. They are 1.6 times as likely to be diagnosed with prostate cancer and 2.4 times as likely to die of this disease.

To conclude, Men’s Health Network is very happy that CMS let the science direct their decision and that the draft guidance provides for on-label access to Provenge as clearly reasonable and necessary. Access to this therapy is critically important to men and their families. CMS needs to ensure that local Medicare contractors do not add barriers to access for Provenge.

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First I have to state I believe this CMS NCD was a much too long and drawn out process: effective medicines should reach people sooner not later. That said I do want to commend your preliminary determination. I believe it is a wise, even-handed, reasonable decision. And I believe leaving off label use up to the doctor and patient was both humanly compassionate and scientifically thoughtful. Considering Provenge has better survival- a wonderful 4.1 month median survival benefit rarely achieved in cancer treatments- far milder side effects and is probably less expensive than less effective and more toxic current approved therapies, I see Provenge approval as a win-win for both patient and the healthcare system. Huzzah!

And if one day Provenge could be used earlier in the disease progression, when patients' immune systems are stronger, well I think this will lead us to healthier patient outcomes sooner and a healthier healthcare system.

Thank you for this opportunity and your time.

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I would like to commend the CMS for issuing a favorable Proposed Decision Memo on Sipuleucel-T (Provenge) Autologous Cellular Immunotherapy Treatment for Metastatic Prostate Cancer. Medicare patients suffering from Prostate Cancer deserve improved treatment options beyond the traditional chemotherapeutic drugs that inflict harmful side effects to the patient. In contrast, Provenge is a safe, effective, clinically proven, FDA approved, breakthrough treatment that activates and trains the body’s own immune response mechanism against Prostate Cancer.

I encourage the CMS to adhere to your Proposed Decision Memo and issue a favorable final determination and favorable final decision memorandum in support of Provenge for our Medicare patients suffering from Prostate Cancer.

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I support Medicare coverage of Provenge for on-label and off-label use.

Provenge provides a safe, innovative, and efficacious treatment for prostate cancer sufferers. In sharp contrast, the only other treatment alternative—Taxotere—almost always has a deleterious impact on the quality of life of the patient.

As a middle-aged male with a history of prostate cancer in my family, I would hope that Provenge would be available to me as a treatment option should the need arise in the future.

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Please support the efforts of the Centers for Medicare and Medicaid Services (CMS) to use autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® to improve health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer.

As a facilitator of prostate health and cancer prevention programs for Black men, there is a need for lost cost treatment options for men that are at high risk, but with few resources. Our organization recognizes the promise of this new therapy and supports the introduction of PROVENGE as a promsing practice to address the gaps that currently exist for low cost treatment.

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I would like to recommend that CMS finalize their very balanced preliminary decision on Provenge.

This treatment is supported by science/statistics and is a novel approach to fighting cancer that could in the future be the primary method to treat cancer — not just prostate cancer but many different types of cancers. Think how odd this approach must look at first glance: a personalized activation of a patient's own immune system (outside of the patient's body no less) to train an individual's immune system to recognize and destroy a specific type of cancer cell !!

I imagine that in the 1790's when Edward Jenner developed a vaccine to defeat smallpox (using the weakened version of the disease cowpox), many people thought this was a crazy/radical idea. And it was ! It also just happened to be a brilliant/clever approach that worked.

Provenge is also a brilliant/clever approach that works ! Let us see where this new technology/idea leads us. Do not let some argue that this is too expensive - the cost of this treatment will come down as it is more widely adopted and benefits of automation and large-scale manufacturing are applied. Who knows? Some day in the future each major city may have a blood donation bank which doubles as a cancer treatment center. "Special this month: donate blood and prostate cancer treatment free (if needed)! "

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I am writing to encourage CMS to limit coverage for Sipuleucil-T to to those patients shown in the published studies to clearly benefit from this treatment, to require patient copayments, to ensure appropriate informed consent, and to require evidence development.

1. The patients enrolled in the research studies that underlie the NCD had the following characteristics, all of which must be present for the drug to be covered by CMS:
   1. The patient is able to come to a treatment center
   2. The patient is capable of providing informed consent
   3. PSA >5.0 ng/mL
   4. Testosterone level <50 ng/dL
   5. Patient is negative for HIV, Hepatitis B or C, or Human T cell lymphotropic virus-1
   6. The patient does not have prostate cancer metastases to liver, lung, brain, ascites, or pleura
   7. The patient has no pain requiring opioids
   8. The patient has an ECOG performance class of 1 or 2.
   9. The patient have no pathologic fractures and no spinal cord compression
   10. No recent infection or fever
   11. Prognosis >6 months
2. Medicare should require a patient co-pay for all eligible beneficiaries (excluding those on Medicaid)
3. Medicare should ensure that all patients being treated with this medication give informed consent, which involves enumerating all substantial risks of the treatment and offering alter approaches to treatment, including palliative care.
4. Medicare should require evidence development with all use of this treatment, whether on or off label

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I strongly support The Centers for Medicare and Medicaid Services (CMS) draft determination that the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication under 1862(a)(1)(A) of the Social Security Act (the Act).

In addition, I recommend that the final national coverage determination removes any ambiguity between the clinical trial enrollment criteria and the FDA approved label to insure access to Provenge for the men in need.

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From 1998 to 2002, the median age at diagnosis was 68 years. The percentages of people diagnosed with prostate cancer based on age were as follows:

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CMS/Medicare support for Provenge is fundamental to improving both the outcomes and the cost of cancer treatment in this country and around the world. Such a revolutionary change in treatment vs current alternatives must be supported and encouraged. This is not just a question of prostate cancer, but all cancers. The possibility of training ones own immune system to fight these horrible and costly conditions must be allowed to evolve and continue to be researched and deployed.

Supporting Provenge is not only compassionate, but also makes good economic sense.

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I am writing to encourage the full coverage of Provenge for the treatment of metastatic prostate cancer. By full I mean to include off label coverage.

Often, by the time a person receives the full barrage of treatment on his way to hormone-resistant prostate cancer, several hundred thousands of dollars are spent. Biopsy, surgery, radiation, hormone therapy, and chemotherapy, are all expensive. The use of Provenge and other such treatment could dramatically improve outcomes both physically and economically.

I ask you to support and cover the use of this treatment. 200,000 families a year are depending on you.

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Provenge represents a new paradigm in treating prostate cancer that is the most efficacious therapy EVER for treatment of this virulent disease. Not only is Provenge the most efficacious treatment, but it comes with the fewest number of side effects. It is an understatement to say that the future of this therapeutic platform is bright both for earlier stage prostate cancer as well as cancer in other organs of the body. To deny coverage of this groundbreaking treatment based on a one-time 93k price tag would be simply silly for a variety of reasons outlined below. Claims aiming for the denial of Provenge made by others such as Dr. Lynn seem to be driven by personal interest rather than the real interest of the matter at hand—the patients. This is shameful. Perhaps such selfish people such as Dr. Lynn should adopt Dendreon's motto of "patients first". I fully endorse coverage for the following reasons:

1) Chemotherapy is awful. 50%+ of prostate cancer patients choose to forgo therapy (and consequently choose death) in lieu of taking Taxotere. Its non-selective mode of action that causes debilitating side effects by killing endogenous healthy cells is simply unacceptable. To choose death over taking Taxotere speaks volumes.

2) All things considered, 93k is comparable to other treatments. Any claims to the contrary are unsubstantiated by facts (and in many cases self-serving, Dr. Lynn, Pazdur, et al.)

3) Immunotherapy using Dendreon's technology platform (or similar) has a great probability of being expanded into other cancers. Provenge is a 1st in class therapy—imagine a situation where immunotherapy of lung, breast and/or any other cancer are all FDA approved. Denial of this based on $$ is ludicrous and would be detrimental to future advancements in the treatment of human disease that will substantially increase net benefit to our healthcare system.

4) The benefit of Provenge is most likely more than 4.2 months. Patients were not followed up on after the trial ended. This means that those alive after 3 years were not added to the median lifespan. In addition, due to ethics and trial setup, the placebo arm was crossed over to the Provenge arm. This ended in Provenge essentially competing against itself until death which makes the 4.2 month survival advantage even more remarkable. Taking these factors into consideration, the survival benefit that is viewed as the gold standard of oncology treatments is more than likely significantly higher for Provenge.

I enthusiastically recommend and support full CMS reimbursement for Provenge with the conviction that this new immunotherapy approach will revolutionize the way cancer is treated. The benefit to prostate cancer patients is simply undeniable and will only get better. It is an investment that will most certainly bear fruit.

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I am deeply concerned that the proposed decision would cover Provenge for ALL patients with castration-resistant metastatic disease when the trials excluded all patients with an ECOG status of 2 or higher and all patients with lung, brain, or liver metastases. It seems very possible that this treatment, which can have quite significant side effects, may actually do more harm than good for such patients, and there is certainly no evidence of effectiveness for these groups.

I am worried overall by the change in outcome measures in mid-study and the lack of a persuasive rationale for why a treatment that does not slow disease progression should enhance survival. But these issues should make us especially wary of extending coverage of the treatment to a group of patients that was deliberately excluded from the trials.

I therefore urge that if Provenge is to be covered coverage should be limited to patients with an ECOG status of 0 or 1, as in the trials.

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I am an oncologist dedicated to the care of men with prostate cancer.

My concern with this agent is that I cannot explain the major (4-month) survival benefit observed in the Phase III trial based on what was actually observed among treated patients. Almost none of the patients had tumors that shrank, remained stable or grew slower when treated with Sipuleucel-T when compared to the placebo arm and almost none had PSA declines at any time.

This kind of discordance between major survival benefit (by oncologists' standards 4months is a rare achievement) and lack of observable tumor control as judged by tumor shrinkage/drop in biomarkers eg PSA or slower growth, is virtually unprecedented in human neoplasia and therefore requires immense caution in interpretation.

Delayed immunologically-driven responses are offered as the explanation for this unique phenomenon. Thus, the lack of examples of such delayed responses is deeply concerning. From a practical standpoint, how could a physician ever know if a patient benefited from treatment with an agent that didnt control disease longer or make the patient feel better?

There are 2 additional plausible explanations for these findings. The first is that a persisting imbalance in prognostic factors, despite randomization, between these two arms is the major driver of these differential survival outcomes between Sipuleucel-T and placebo groups. Our current prognostic models, applied to these data, are weak enough for such an effect to be missed. We simply do not have the tools to predict biological behavior of prostate cancer that well. If this factor was at play, then it means that Sipuleucel-T has no therapeutic effect at all.

Another explanation for these data is that the subsequent response and disease control with chemotherapy after disease progression on Sipuleucel-T is markedly improved after the receipt of the vaccine through hitherto undefined immunological mechanisms. This is an unstudied but real possibility and if true, would direct a better understanding of this agent and further development of the field critically necessary for more tangible advances.

I believe that given these serious discrepancies, further research into this drug should be mandated. My personal opinion is that patients should be granted access to this drug as long as they participate in properly designed and widely available additional studies to determine if and how this drug truly works. The input of the prostate cancer scientific community independent of the manufacturer would be critical to the design of such trials.

In such studies, my personal opinion is that the drug should be reimbursed to patients participating in such trials, by Medicare, given the survival benefit demonstrated in the FDA-sanctioned studies to date. This would seem to be fair to the company that has taken such risks and efforts to bring this drug this far in development. It should not however be approved for off-label use or outside the clinical trial setting.

Finally, I would like to express my gratitude for the opportunity to express an opinion on this very important subject. Given the tremendous resource crunch in the research field, we need all the resources we can find to fight this and other cancers and it is critically important that we do not make irretrievable mistakes in either direction. It is my hope that these comments are constructive and well-placed.

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I am a urologic surgeon and a fellowship trained transplant surgeon. I fully support CMS coverage of Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (00422N). This is a revolutionary treatment using a patient's own immune cells to specifically target and attack prostate cancer. Castrate Resistant Metastatic prostate cancer is a terminal disease. Thus, this treatment which has been proven to significantly extend survival with mild side effects is a significant step forward not only for prostate cancer, but for the battle against all other forms of cancer. This treatment will help many men who before only had the option of taxotere chemotherapy which has less survival benefit and more toxicity. Please confirm the preliminary assessment by CMS that this is a reasonable and necessary treatment.

Sincerely,
Leonard Liang, M.D.

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I would like to express my strong support on CMS' preliminary decision to allow on-label use coverage of Provenge.

The immutherapy is the future of cancer treatment. Our country needs to take brave steps to encourage innovation.

The 4-month medium survival is quite misleading. In fact, it means half of the patients under Provenge would survive more than 4 months, or even years, than the placebo group. CMS should not deny the hope for about half of the patients.

Also, the high cost of Provenge is misleading. While taking into consideration of other costs, Provenge is comparable to other treatments such as chemo.

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Below are some comments on Dr. Joanne Lynn’s comments posted on 4/16/2011:

1. In scientific drug testing, the entry protocol of a well-controlled randomized blinded trial must be precisely defined to ensure that patients are as similar as possible between the two arms of the trial. Thus, aside from the definition of a disease or disease stage to be treated, the entry protocol of a trial would often include or exclude certain additional patient characteristics. The FDA was well aware of this when they approved a label for Provenge based on the definition of the disease stage to be treated, ie, hormone-refractory prostate cancer and metastatic but still asymptomatic or minimally symptomatic, i.e., not yet on a systemic treatment for pain. A consequence of Dr. Lynn’s suggestion to limit the use of Sipuleucel-T treatment only to patients meeting the exact trial protocols instead of the FDA-approved label would be to put into jeopardy the lives of many patients who could have been saved by Sipuleucel-T.

2. Dr. Lynn was mistaken in asserting that the “Effectiveness (of Sipuleucel-T) is probably overstated” based on her consideration of concurrent health conditions afflicting patients. Note that the trials of Sipuleucel-T were randomized and doubly blinded so that whatever conditions that ailed patients beyond prostate cancer should be equally represented on the two arms of the trial. Thus, the demonstrated efficacy of Sipuleucel-T was due to Sipuleucel-T alone. The pivotal IMPACT trial of Sipuleucel-T showed an extension of 4.1 months median survival time in the treatment arm beyond the control arm. Further, the odds of a patient treated with Sipuleucel-T surviving at 3 years was about one in three comparing to the odds of about one in five for an untreated patient. This level of efficacy coupling with a mild side effect profile was remarkable when compared to the current standard of care, the chemotherapy Taxotere, which showed only a 2.5 months median improvement with possibly delibitating side effects.

3. It was curious that Dr. Lynn’s main concern about the effectiveness of Sipuleucel-T started not with a consideration of scientific evidence but with the statement: “This is a very expensive treatment for a condition that mostly afflicts persons in advanced years,…”. First, the cost of 93,000$ for a Sipuleucel-T treatment is a once-per-life-time cost. This is to be compared with the cost of chemotherapy that must be repeated over many months, perhaps years, and often end up far more expensive when the additional costs to treat side effects are totaled. Second, prostate cancer affects a large number of patients in their sixties and seventies who, nowadays, may normally live for another 20 or more years if their disease could be treated in time. Many of these “advanced years” patients as Dr Lynn called them are not “living with dementia and frailty” as she alleged. They often opt to avoid the side effects of chemotherapy because the lost of quality of life could be as bad as the cancer pains. But, untreated or treated with chemotherapy could eventually lead them to expensive hospitalization and/or cost of life. Sipuleucel-T is not just an attractive treatment choice for these patients thanks to its benign side effects but may also be the only choice possible. It is uncompassionate for Medicare to deny patients that choice.

4. Current law prohibits Medicare from using treatment cost in deciding whether or not to provide a treatment to patients. Nonetheless, if Medicare wishes to address Dr Lynn’s concerns about the cost of Sipuleucel-T at a systemic level, it should do so in a larger context by comparing Sipuleucel-T with other cancer drugs that Medicare patients may take. The advantages that Sipuleucel-T provide are (i) its once-per-life-time cost is compatible to or even cheaper than the yearly cost of a number of other important cancer treatments (e.g., Avastin, Herceptin, Erbitux, etc.) that Medicare is already paying for, (ii) the treatment extends life of patients beyond any other currently available treatment for late stage prostate cancer, and (iii) it does so with minimal side effects, hence preserving and enhancing quality of life to patients. As such, a patient treated with Sipuleucel-T may require far less follow-on treatments, thus resulting in an overall saving to the system.

5. Lastly, it should be pointed out that, aside from wrongfully denying patients from getting treated for a terminal disease, a consequence of Dr Lynn’s suggestion to restrict usage of a drug/treatment strictly to the conditions of the relevant trials would have a devastating effect on medical innovation. Her suggestion, when applied to other drugs, means that every useful treatment would have to go through many sequential trials for different combinations of conditions separately, no matter how trivial the differences are between combinations. The costs to do that would be so prohibitive that the development of new drugs for untreatable diseases would be severely curtailed.

In summary, I believe that the recent proposal by CMS to allow coverage of Sipuleucel-T based on the FDA-approved label while leaving the decision of off-label usage to local contractors is the correct course of action. The FDA, with vast experience in assessing clinical trial data to approve many important life-saving oncology drugs, had thoroughly checked the data available on Sipuleucel-T and approved it for patients meeting the description of “Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer”. This is the population of patients that Medicare should provide benefit to. Adding further constraints to limit patients and adding more requirements for unnecessary documentation as Dr. Lynn suggested is unreasonable. In fact, such a decision process would incur more cost to the system due to further unneeded testing and added burden to physicians and patients. And, last but not least, not allowing the use of a treatment to patients who would benefit from it, especially those determined eligible by the foremost authority in the land, the FDA, is both uncompassionate and wrong!

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Dr. Lynne is way off with her Provenge comments!

I support aspects of Dr. Lynne's writings about palliative and end of life concerns; but her approach to Provenge makes no sense.

Provenge is not only life extending (with retention of full quality of life - like coaching little league for years after treatment) but it is not a last line of treatment. Taxotere and possibly abiraterone and others will follow Provenge treatment.

A hospice is to end of life treatment as a retirement home (or managing one's own home) is to Provenge.

Abstracting from IMPACT, neither CMS nor Dr Lynne should betray the hopes of the 40% who will live for 3 years or more after Provenge with an unsophisticated use of the unreliably conservative 4.1 month median.

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This is a ground breaking treatment for prostate cancer, it helps patients live longer without the terrible side effects of chemo, and must be approved.

Provenge will become the standard treatment for prostate cancer against which all other drugs/treatments will be compared. It is the least damaging of all "chemo" treatments for this terrible disease and may actually give better results by being given earlier rather than later in the progression of the cancer.

Many patients refuse chemo because of the dreadful side effects caused by chemo treatment. Provenge has virtually no side effects, slight chills, fever and headache are the side effects some patients reported, but almost all of these were minor and lasted no more than a day or two after treatment. Compare these side effects to those of chemo treatment. The difference is dramatic to say the least and clearly puts Provenge ahead of the rest.

Some posters seem to be unaware that the 4 months survival benefit so often quoted is actually the MEDIAN survival benefit and not the AVERAGE. By definition a median of four months indicates that half the men lived more than an extra 4 months and some patients actually lived for several years. Clearly those posters so persistent in referring to the four months survival benefit as the "average" have ulterior motives or are in need of updating their middle school math skills.

The CMS review does not and should not consider cost when approving a new treatment. However, if we really must take into account the cost for Provenge we must also take into account the cost of treating the patient for the terrible side effects of chemo. If one does that Provenge still comes out on top. The total, entire cost for Provenge treatment consists of a SINGLE, one time payment of $93,000, per patient. That's it. This is not a recurring payment. So why do some posters indicate that this is a recurring payment every year. Do they have a hidden agenda?

To conclude, taking Provenge means a patient lives longer with virtually no side effects. The quality of a patient's life is light years better than that of a patient treated with chemo. Who wants to live longer if the quality of life is so poor because of the side effects from chemo treatments? The possibility that Provenge may provide much more benefit by being given earlier in the progression of prostate cancer should also be explored. Finally, the important question to ask is not should we approve Provenge, the question should be why was Provenge not approved years ago?

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Thank you CMS for your well-reasoned draft proposal on Provenge. Please formalize this proposal in your final decision on CMS coverage.

We are in a fiscal environment where Medicare and Medicare must be prudent in their health care expenditures. However, it would be a mistake to curtail the use of a revolutionary approach to prostate cancer that advances beyond the "burn or poison" treatments of radiation or chemo and offers patients superior treatment with little side effect. In addition, it is important to reinforce the US position as the leader in the development of new medicines and new medical treatments by supporting breakthroughs like Provenge.

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As a retired scientist who have worked 30 years in biotech research in universities and private pharmaceutical companies, I know research to find cancer cure is a slow process. Now Provenge is a truly break-through treatment for prostate cancer. It utilize patients' immune system to fight the disease. Unlike chemotherapies which use toxic chemicals to kill the cancer cells as well as the healthy cells and cause miserable side effects, Provenge prolongs life and gives patients good life quality.

To encourage further research in autologous cellular immunotherapy for prostate cancer as well as other types of cancer, CMS should not only approve Medicare coverage for on-label usages of Provenge, but also encourage the early use of Provenge to fight early stages of Prostate cancers.

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I believe my friend Saul Kerpelman said it best regarding Dr. Joanne Lynn -

First, I realize this is a public comment period and employees of CMS are part of the public, but I must say it smacks of impropriety for a CMS doc to be airing opinions in this forum. If CMS is considering the appropriate thing to do behind closed doors—as the regulations seem to contemplate—it seems inappropriate for less than all of those involved in the decision-making process to be publicly expressing their opinions here. If it is sour grapes, because she is expressing a dissenting opinion, that too seems wrong, since she already had her chance to state her position and is just undermining confidence in CMS.

Then, substantively, her position seems very biased to me—not to mention illegal, in that it seems to be based primarily upon price considerations, as well as being premised upon a failure to grasp the underlying scientific facts. The enabling statute for Medicare of course requires coverage of treatments which are "reasonable and necessary", meaning likely to benefit the health of the Medicare population. Price is not allowed to be a factor, yet she goes on and on about value and cost benefit and co-pays, etc., essentially taking the position that the "tiny" benefit of Provenge is not worth the cost for an already dying population, and therefore its availability to the Medicare population should be restricted as much as possible. Is CMS really wanting to revive the "Death Panels" debate??

Not to mention that suggesting that the benefit from Provenge is "small" seems to evidence a lack of understanding of the data. The survival benefit of Provenge is the largest EVER in this population. Dr. Lynn seems unaware of this. Perhaps she is falling into the "just 4 extra months of life" trap, but this too is fallacious, as 4 months is the median survival benefit and by definition half the men live MORE than an extra 4 months—many for years. One would hope and expect that a physician employed by CMS would have a better understanding of statistical concepts. Perhaps she has not looked at the data showing a 40% improvement in 3 year survival in men who were treated with Provenge. She also asserts that the trials likely overstated the benefit of Provenge, when in fact the recently published Duke University analysis of the data instead suggests that the trials actually UNDERSTATED the benefit of Provenge, since the cross-over salvage product seemed to confer its own benefit to the "placebo" group—which of course was not really placebo, but delayed Provenge.

I say that her post seems biased because it seems to me to be based upon age discrimination—which seems especially strange for a doctor working for CMS and thus Medicare, which is charged with improving the health and lives of older patients. Perhaps this is a remnant of her background in palliative care for the dying, but I must say that my reading her attitude of "just let them die without pain" evoked outrage. How easy for her to say about someone else's life.

Older men with prostate cancer deserve every chance to live longer. That's not just my opinion and public comment—it's the law. And it is pretty shocking to read comments from a doctor employed by CMS pretty blatantly arguing that Medicare should not obey the law, but instead, for economic reasons, should be restricting the availability of a breakthrough life-extending treatment.

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I support Medicare coverage of Provenge both for on and off label.
I feel Dr. Lynn's post seems biased because it seems to me to be based upon age discrimination—which seems especially strange for a doctor working for CMS and thus Medicare, which is charged with improving the health and lives of older patients. Perhaps this is a remnant of her background in palliative care for the dying, but I must say that my reading her attitude of "just let them die without pain" evoked outrage. How easy for her to say about someone else's life.

Older men with prostate cancer deserve every chance to live longer. That's not just my opinion and public comment—it's the law. And it is pretty shocking to read comments from a doctor employed by CMS pretty blatantly arguing that Medicare should not obey the law, but instead, for economic reasons, should be restricting the availability of a breakthrough life-extending treatment.
I am sure if Dr. Lynn was faced with a loved one of her own, that had cancer, she would not feel this way. Of course if she did that would be pure evil.

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I have been following the cancer immunotherapy field for years. I would like to see the practice of treating prostate cancer move towards using Provenge, but testing for upregulation in CD-54 after the second treatment and not continuing the treatment if there is no increase in CD-54 or an otherwise measured response from the immune system.

I want to see a balance between encouraging innovation (which stimulates the economy, exports and job creation) and discouraging the overuse or misuse of drugs and medical technology.

I believe CMS’ preliminary decision recognizes the evolving nature of the technology. With the exception of testing for upregulation in CD-54, the proposed CMS decision hit the right note:

And that, at a high level, is where the policy changes should be directed. Is medical care a “right”? what are the appropriate capitation levels? Should they be age, mobility or cognition based? How can “means testing” be more effectively utilized?

This is American capitalism at work. A new product or new idea comes out, and the people that created it and moved it to the market get compensated for their effort. This encourages others to attempt to do the same, with the knowledge that most fail. Yet, seeing rewards, like lemmings we keep trying.

It took Dendreon, nearly 20 years to finally reach success. The company has increased the number of employees by a factor of five in the past 12 months. The numbers are small, but helpful, given the overall economy. Dendreon’s scientists are creating intellectual capital as they expand ACI; in turn, that intellectual capital is recognized by Wall Street and is creating wealth - in an environment where many people have recently experienced meaningful wealth destruction.

In my opinion, before long the window for funding biotech companies will reopen, and many small firms will start the process again. If so, this is very good for the creation of well-paid technical and professional jobs in America.

The authors recognized the evolving nature of this particular technology and treatment.

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I'm encouraged that CMS has not ruled out off label use for Provenge. The trials that were approved by the FDA targeted men with hormone refractory prostate cancer (androgen independent). These men were very sick and even with their compromised immune systems Provenge extended survival by 4.1 months median and increased 3 year survival by 40%. These numbers are even more impressive once you take into consideration that crossovers were allowed in these trials. There is some statistical evidence that suggests the median survival is closer to 14 months.

Covering Progvenge for it's FDA approved indication when the previous standard of care was chemotherapy is an easy decision in my opinion, but allowing Provenge to help men earlier in the prostate cancer cycle while they are healthier is the optimal one.

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I feel like I have to respond to the recent negative comment by Dr. Lynn.

First, I realize this is a public comment period and employees of CMS are part of the public, but I must say it smacks of impropriety for a CMS doc to be airing opinions in this forum. If CMS is considering the appropriate thing to do behind closed doors—as the regulations seem to contemplate—it seems inappropriate for less than all of those involved in the decision-making process to be publicly expressing their opinions here. If it is sour grapes, because she is expressing a dissenting opinion, that too seems wrong, since she already had her chance to state her position and is just undermining confidence in CMS.

Then, substantively, her position seems very biased to me—not to mention illegal, in that it seems to be based primarily upon price considerations, as well as being premised upon a failure to grasp the underlying scientific facts. The enabling statute for Medicare of course requires coverage of treatments which are "reasonable and necessary", meaning likely to benefit the health of the Medicare population. Price is not allowed to be a factor, yet she goes on and on about value and cost benefit and co-pays, etc., essentially taking the position that the "tiny" benefit of Provenge is not worth the cost for an already dying population, and therefore its availability to the Medicare population should be restricted as much as possible. Is CMS really wanting to revive the "Death Panels" debate??

Not to mention that suggesting that the benefit from Provenge is "small" seems to evidence a lack of understanding of the data. The survival benefit of Provenge is the largest EVER in this population. Dr. Lynn seems unaware of this. Perhaps she is falling into the "just 4 extra months of life" trap, but this too is fallacious, as 4 months is the median survival benefit and by definition half the men live MORE than an extra 4 months—many for years. One would hope and expect that a physician employed by CMS would have a better understanding of statistical concepts. Perhaps she has not looked at the data showing a 40% improvement in 3 year survival in men who were treated with Provenge. She also asserts that the trials likely overstated the benefit of Provenge, when in fact the recently published Duke University analysis of the data instead suggests that the trials actually UNDERSTATED the benefit of Provenge, since the cross-over salvage product seemed to confer its own benefit to the "placebo" group—which of course was not really placebo, but delayed Provenge.

I say that her post seems biased because it seems to me to be based upon age discrimination—which seems especially strange for a doctor working for CMS and thus Medicare, which is charged with improving the health and lives of older patients. Perhaps this is a remnant of her background in palliative care for the dying, but I must say that my reading her attitude of "just let them die without pain" evoked outrage. How easy for her to say about someone else's life.

Older men with prostate cancer deserve every chance to live longer. That's not just my opinion and public comment—it's the law. And it is pretty shocking to read comments from a doctor employed by CMS pretty blatantly arguing that Medicare should not obey the law, but instead, for economic reasons, should be restricting the availability of a breakthrough life-extending treatment.

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I strongly urge the CMS to support the use of Provenge for use as the doctors see fit - both on label and off label use.

As a pastor, I have seen the ravages of cancer as well as the ravages of cancer treatments.

This treatment has very mild side effects and helps the patient live with dignity and freedom. Besides all that - it works quite effectively!

Off label use is important to me because it very well might be beneficial to use this treatment in earlier stages of the cancer and thus save medical expenses and help the patients continue productive lives.

Let the doctors select treatment choices with every tool available. Please allow them to practice medicine with Provenge as they determine is the best - both on label and off label.

Please call me if you have any questions about this perspective. I do not write as a medical professional, but as a pastor who cares for the overall well being of those in my community and in our nation.

Thank you for your time and consideration.

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I fully support CMS approving the use of Provenge for men suffering from late stage prostate cancer as well as earlier use of Provenge for the men with an earlier stage of this horrific decease.

Provenge has gone through four different PIII trials and has been reviewed extensively by the FDA for it's effectiveness. Plan and simple, it works!

When a 'drug' helps built one's own body fight this crumpling decease without the horrendous side affect of chemo AND adds additional months to a man's life, why won't it be supported by the CMS? Costs? When compared to ALL of the additional expenses of chemo including hospital stays and anti-nausia drugs, Provenge is actually less costly than the alternative without losing the "Quality of Live". This sounds like a win, win situation to me!

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I am writing in SUPPORT of CMS coverage for Dendreon's Provenge. I believe CMS should cover Provenge 100% for both on AND OFF label use. Citizens of the U.S. deserve such leading edge medical breakthroughs for the 21st century. Considering the side effects of Provenge relative to chemotherapy the costs of Provenge is less than the comprehensive costs attributed to chemotherapy.

The chemo industry and captured doctors will be the entities that fight tooth and nail against Provenge because it is THE GAMECHANGER for their industry. They know and you know it. The future of cancer treatment starts with Provenge and CMS should not delay any further in approving full reimbursement - both on and off label.

The advantages substantially outweigh the negatives for Provenge reimbursement. It is an investment in the medical community on a number of levels.

Again, please approve full coverage for Provenge - both on and off label use.

Respectfully submitted,

—Lee Adams

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Provenge,studied and reported as prolonging usefull life and greater survival than any other medication to treat androgen deprived patients with metastatic prostatic cancer, ought to have the opportunity to have the potential benefits if they choose.
Consider that this choice is no different than that faceing thee potential liver or heart transplant patient, whose life is prolonged by by having surgery to replace the ailing organ. We are not talking about cure here, only palliation.

This provenge is less toxic than other palliative medications for these patients... and has better survuval statistics. Sowhere is the beef?
Approve and continue to require data on the patients as a method of showing your concern for the patients welfare, since this treatmenat is so costly.

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I am not sure Dr. Joan Lynne should even be allowed to post a comment being a CMS employee, but in a way I am glad since it gives me the opportunity to respond.
Joan main concerns were the effectiveness and cost of Provenge.
Effectiveness: Provenge had to go through multiple trials and a high statistical bar for effectiveness set by the FDA. It passed with flying colors. I’d like Joan to stand up and tell the close to 30% of patients still alive 3 years after receiving Provenge that the “EFFECTIVENESS IS PROBABLY OVERSTATED”.
Cost: When cost of treating side effects of Chemo treatment is included, the Provenge cost is comparable, and when normalized to the amount of extended life, then Provenge is a cost reduction over the chemo current standard of care.

I’d also like Dr. Joan Lynne to think back to the days before Penicillin was invented to treat infections. In those days if any limb got infected, they cut it off. Many doctors were against the anti-biotic and advised their patients to get their limbs cut-off.
Dr. Lynne, what would you have advised your patients if their foot got infected?

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I wish to directly respond to Joanne Lynn Md's comments.

First, There is an obvious bias in this doctors thinking and analysis. She obviously does not practice clinical medicine for prostate cancer. Her work has focused on end of life isues and terminal care. While I applaud her accomplishments the simple fact is that those patients receiving provenge are far from death's door.
I would challenge some of her claims:

First she states that "Most actual patients would not have had sufficiently robust performance status, and many would not have been competent for consent. " (to receive provenge on the trials) in other words the patients on the dndn trials represent only a small biased sample of the general AIDPC population and are not representative of the majority of patients out there.

The fact is that hormone refractory patients still live for a considerable amount of time. Their performance status is nearly always more than adequate for provenge. I have treated several thousand prostate cancer patients in my career and I can say that the majority of incuable prostate patients are not in the condition portrayed by Dr Lynne when they first become eligible for provenge.

I believe Dr Lynne"s is biased given her background in paliative care and the dying patient The simple fact is that 27% of patients were still alive 3 years after receiving provenge. Furthermore, high risk patients with high gleason grades benefited and a high percentage of patients on the control arm received provenge after the trial was completed.

Her comments contain many other biases and dwell on social economic issues far beyond the scope of the present CMS review process. This CMS process does not include recommendations for tracking copays, keeping a registry of all eligible patients or Having CMS design a special consent outlining the limited benefit and (in her opinion) terrible side effects (rigors) and expense from provenge.

She believes provenge is a "low-benefit, high cost treatment." Her comments would lead us to believe that provenge is not warranted for the majority of androgen independent prostate cancer patients because it affects feeble, old, incompetent men with not enough money to pay for the copay. This is simply not the case.

Joanne Lynn had directed the SUPPORT Study to chair the IHI End of Life Care Collaborative. Lynn made her mark in the 1980s by developing guidelines for withdrawal of treatment. In a Hasting Center Symposium on May 20, 2008, she said, “We need to build a social consensus drawing on a new paradigm that tailors care to the new reality of dying—which is after a long, chronic illness. Not only is it the right thing to do, it makes good business sense.”

a June 1997 NY Times story describes what Lynn believes about total sedation and withholding and withdrawing life sustaining treatment. “When a patient is ready to die, I can stop nutrition and hydration, I can stop insulin and ventilation, I can sedate them. I can creatively collaborate with the forces of nature. But if they really want to control being dead tomorrow at 10, I cannot promise that.” "

While I agree that approach is valid under certain circumstances, I think it is inappropriate to extend this philosophy to androgen independent prostate cancer patients. I do not believe as does Dr Lynn that the FDA's label for provenge is a "substantial generalization that the FDA adopted and that this proposed coverage rule would accept." The FDA made their label recommendations after careful analysis, years of input into the trials and the subsequent analysis of the clinical trials that led to the approval of provenge.

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I’m writing to express my support and gratitude for the CMS’s recent national coverage decision draft with respect to Dendreon’s prostate cancer treatment Provenge.

As I’ve stated in a previous comment (7/8/2010), I’ve seen firsthand the frequently ravishing effects that chemotherapy has had on friends and family afflicted by various cancers, and have followed the Provenge story since the results of the Impact Study were first released.

With its clearly significant survival advantage coupled with a safety profile far more tolerable than the previous standard of care (Taxotere), my view is that Provenge should be the first choice of the medical community tor treating metastatic castrate resistant prostate cancer. I believe that the superior survival advantage combined with such a safety profile actually mitigate what is viewed by some to be a high price for the treatment, as many of the ancillary costs associated with Taxotere treatment (e.g., hospitalization for treatments of side effects) would be minimal or non-existent with Provenge.

Finally, I also wish to commend the CMS on their proposed decision to leave the door open for possible off-label usage. Given the initial evidence of Provenge’s superior 3-year survival advantage (40% better than the control group) with its subjects in the clinical trials (most of whom at the time represented the “sickest of the sick”), it is not unreasonable to believe that Provenge might be even more effective if used at an earlier stage of the cancer.

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Please cover Provenge. I have read some comments written by ignorant people who spew misinformation about how long the patients survive and their quality of life after treatment. The facts are that there are some patients who have been living for years after taking Provenge. I have heard stories of men being treated on a Tuesday and they are out on the golf course by the weekend. The quality of life is so much better than the alternative toxic treatments plus there are no expensive hospital stays and other costly medications to manage the side effects. We are just at the beginning of this revolutionary fight against cancer. It will only get better. Thank you for keeping this process transparent.

Mike Kearney
Spokesperson for CareToLive, a not for profit corporation
PublicRelations@CareToLive.com

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As a wife, mother and concerned citizen I applaud the decision of CMS to cover Provenge through Medicare. This life-extending treatment is a safe alternative to current treatments which are so awful that many men choose to die rather than suffer the side-effects.

These extra months/years you allow us with our loved ones are priceless. To allow a father or grandfather at a child's graduation, their presence at the birth of a child or grandchild, their loving eyes present to watch lovingly over a family should not be open for debate. Particularly when the FDA has deemed that this treatment is the standard of care for this stage of the disease. And always remember that it is you or your loved ones that may need this treatment next...

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Just as so many Americans have, I too have lost loved ones to painful deaths due to cancer. Mindful of this, I respectfully urge CMS to approve Provenge and withdraw the NCA now.

Dendreon has provided us with a stellar moment in the war agains cancer with its autologous cellular immunotherapy (PROVENGE). Provenge boosts an individual's own immune system to fight cancer cells. No poisonous chemo required!

America has waited a long time for an advance in the cancer fight. Provenge has proven to have mild, short-term side effects; provides a superior quality of life; extends life! Hopefully Provenge will be allowed earlier availability too in order to boost the immune system from a less compromised state. That would be terrific.

Provenge is a major breakthrough. I trust you will approve its use. America is waiting for this humane advance in the fight against cancer.

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This paradigm provides for an highly valuable treatment shown to extend men's lives from 4+ months to several years. It has been shown that if the man's immune system has not been completely destroyed.. it will function again, after PROVENGE is given - the way it formerly did, and will stop the proliferation of the cancer cells.

Hopefully, PROVENGE will be allowed to be used EARLIER - "before" a person's Immune System has been majorly compromised. This treatment is more effective than than any other treatment at the approved stage (Taxotere), but it's median Survival is TWICE as long! Taxotere's median survival is only 2 1/2 months!

Use of PROVENGE, not only saves a person's QUALITY of LIFE, because the common side effects are only a few days of mild chills and fever - but it also cuts down on the COSTS of HOSPITAL stays from the side effects of chemo and radiation! Many drugs, after chemo and radiation - are needed for nausea, pain, mouth sores, feet pain, liver toxicity, diarrhea and the many permanent and temporary side effects that are common to the toxicity of the Chemo and radiation! These expenses can potentially FAR outweigh the cost of the three infusions of PROVENGE!

Hopefully this is only the beginning of using this type of Vaccine / Immunotherapy - to help a person get rid of cancer! Maybe in the near future, people can get a booster after a number of years - to stave off the cancer.

Please allow this wonderful treatment to be used.. and please allow it to be used (soon) earlier - to prevent numerous deaths (while also saving on the costs of Chemo and Radiation's side effects).

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I am posting my unconditional support for the CMS decision to cover Provenge for men with cancer. There is no question that this is the right decision and it opens the dcor to the use of immunotherapy for all types of cancer.

The data is conclusive that Provenge is beneficial to cancer patients and that Medicare needs to not only cover "on label" reimbursement, but encourage "off-label" usage as well. The use of the body's own immune system to battle cancer is clearly a ground-breaking technology and it needs to be encourage.

In addition, the cost of Provenge is reasonable when all the costs of chemotherapy...additional hospitalizations and side effects are considered.

I would urge the committee to encourage additional studies and use of Provenge on earlier-stage patients as the data seems to support the fact that immunotherapy works best when given at the earliest possible time.

In conclusion, I urge CMS to implement the draft memo as its final decision in June.

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To the Committee ...

I have been praying for YEARS - for the type of treatment that PROVENGE offers to Cancer victims!! I lost [PHI Redacted] to this HIDEOUS disease - and had to watch them suffer and die earlier, because of the destruction of their immune systems, and horrendous and barbaric side effects of the TOXIC Chemo and Radiation that was forced on them!!

Why does a patient who is suffering, then have to be TORTURED ??

This new paradigm - which uses the patient's own Immune System to attack the Cancer Cells - is the most HUMANE treatment we've EVER had! Please don't stop it's entrance into the Humane and Progressive treatment of Cancer.. This valuable treatment has been shown to extend men's lives from many months into YEARS! This has been shown to be TRUE now! If the man's immune system has not been completely destroyed.. it will function again, after PROVENGE is given - the way it USED to,, and will stop the proliferation of the cancer cells!!

Hopefully, PROVENGE will be allowed to be used EARLIER - "before" a person's Immune System has been majorly compromised. This treatment is not only VERY EFFECTIVE - more effective than the only other treatment at the approved stage (Taxotere), but it's median Survival is TWICE as long! Taxotere's median survival is only 2 1/2 months!

Use of PROVENGE, not only saves a person's QUALITY of LIFE, because the common side effects are only a few days of mild chills and fever - but it also cuts down on the COSTS of HOSPITAL stays from the side effects of chemo and radiation! Many drugs, after chemo and radiation - are needed for nausea, pain, mouth sores, feet pain, liver toxicity, diarrhea and the many permanent and temporary side effects that are common to the toxicity of the Chemo and radiation! These expenses can potentially FAR outweigh the cost of the three infusions of PROVENGE!

Hopefully this is only the beginning of using this type of Vaccine / Immunotherapy - to help a person get rid of cancer! Maybe in the near future, people can get a booster after a number of years - to stave off the cancer.

Please continue to allow this wonderful treatment to be used.. and please allow it to be used (soon) earlier - to prevent numerous deaths (while also saving on the costs of Chemo and Radiation's side effects).

I truly appreciate your consideration.

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I urge CMS to approve Provenge for coverage; it has proven itself to the high standards of the FDA; received FDA's approval and compares favorably (if not better) with the the TOTAL cost of the sole chemo treatment.

I am a life-long taxpayer; my government made a contract with me decades ago to provide medical care in my retirement years.

I am a covered Medicare recipient; my family has a history of prostate cancer and there are 4 brothers at risk today.

The Quality of Life and MEDIAN (not average) survival are far superior to chemo.

Consider my comments favorable to a positive CMS decision.

Respectfully submitted,

Tony F.

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I strongly support the recommended national coverage decision draft regarding the prostate cancer vaccine Provenge by Dendreon. I follow Provenge development and believe that this is a real breakthrough. Do the right thing and many ofter similar drugs will follow. Many men who currently have no other option (chemo is not an option for many of them) are desperately waiting. Please do the right thing and provide whatever approvals are required to help these men.

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I am a health economist with 15 years of pharma- industry experience submitting reimbursement dossiers to health insurance authorities in America, England, Scotland, Germany, France, Japan and South Korea. So I speak with some authority with regards to worldwide insurance reimbursement standards, whether they be cost-effectiveness, comparative-effectiveness or 'reasonable and necessary' standards.

First of all, with regards to the elephant in the room i.e. cost. I can say with confidence that Provenge would be considered cost-effective in even the strictest reimbursement environment i.e. England. The highest hurdle for cost-effectiveness in the world is found at England's National Institute for Clinical and Health Excellence, or NICE. Taxotere was subjected to NICE's strict cost-effectiveness hurdle and was approved. NICE considers the full annual cost of taxotere treatment in its assessment i.e. drug cost + incidence of drug-related side-effects and associated treatment costs. Also at NICE, the impact on quality of life of the drug treatment is evaluated. So in applying NICE's strict criteria for economic value and utilizing the Taxotere economic model, one can see that Provenge would also be approved because: 1) the total annual cost of Taxotere+side-effect costs is approximately equal to the total cost of Provenge 2) the quality of life impact is much worse for Taxotere compared to Provenge and 3) Provenge doubles the improvement in months of survival vs. Taxotere.

References for the total cost of Taxotere and comparative effectiveness of Taxotere vs. Provenge can be found at:

http://www.health.gov.au/internet/main/publishing.nsf/Content/pbac-psd-docetaxel2
http://www.miamiherald.com/2011/02/08/2055167/new-therapy-fights-prostate-cancer.

and the Taxotere NICE review:

http://www.nice.org.uk/guidance/index.jsp?action=download&r=true&o=33353

So in response to the concerns that Provenge is just too costly for Medicare, I would respectfully refer these concerned citizens to the data already provided by Taxotere at NICE, and the prima facia evidence that Provenge provides equal or greater cost-effectiveness compared to Taxotere given its nearly equal total cost, superior efficacy and superior quality of life impact.

As for the US and Medicare's criteria of 'reasonable and necessary', the CMS team has reached the obvious conclusion that Provenge is reasonable and necessary by applying its standard fairly and thoroughly as per its legislative remit in the NCD process. I say 'obvious conclusion' because as we can see when reading the Freedom of Information releases documented at the CareToLive site for prostate cancer activists, the regional Medicare offices never raised a single doubt as to whether Provenge was reasonable or necessary. Every single regional Medicare office concern was related to administrative minutia of how to reimburse the multiple step process associated with Provenge administration i.e. 3 separate leukapheresis procedures, and later 3 infusions of the blood product Provenge.

Questions about how to reimburse this multiple step process then began to fill the email docket of the CMS regional offices. But did such questions really require a costly, long drawn out National Coverage Determination process and associated National Coverage Analaysis and related Health Outcomes study and related MEDCAC panel?

I've overseen the production of health outcomes studies and the gathering of expert panels and this is not an inexpensive endeavor. A typical outcomes study costs $200,000 and flying 15 medical experts for a 1 day panel meeting can cost an additional $100,000. Presumably, several CMS employees have spent considerable time overseeing this Provenge NCA process, perhaps costing the taxpayer an additional $200,000.

None of these taxpayer-funded NCD-related costs come close to the impact this NCD has had on patients and family members. As many urologists and oncologists attested to in the first set of public comments for this Provenge NCD, reimbursement uncertainty for Provenge caused by this NCD process, has lead many patients to delay seeking Provenge treatment over the last 6 months.

So the question must now be answered "was this NCD process for Provenge necessary and was the cost and mental anguish for patients worth this benefit of this NCD process"?

Provenge stands nearly alone among new cancer treatments in the past 20 years that have extended survival by greater than 4 months. Only 3 other cancer drugs have been shown to increase survival by more than 4 months in the past 20 years of what many consider to be the golden age of cancer treatment discoveries. And Provenge stands alone at the top of all cancer treatments with respect to its benign side-effect profile. No cancer treatment in the long history of cancer research has such mild side-effects such as flu-like symptoms lasting 2 days, which by the way, only a fraction of Provenge patients experience, many experience exactly zero side-effects.

So with 15 years of pharma-industry experience working with reimbursement authorities from around the world and thus, becoming intimately familiar with the legislative remit and procedures of these reimbursement agencies, I believe that the CMS National Coverage Determination Process for Provenge was a completely unnecessary and inappropriate application of the purpose and intent of the NCD process.

Even one of the MEDCAC expert panel members, Pearl Moore, when interviewed by the Pittsburgh Jewish Chronicle, expressed her confusion as to why this NCD process was even initiated for Provenge. As she states "We were confused, too. It is unusual for Medicare to call a panel to repeat this.”

You can see her interview at: http://www.thejewishchronicle.net/view/full_story/10507815/article-Pittsburgher-named-to-presidential-advisory-committee?instance=home_news_metro_right

It is my firm belief then, that this decision was politically driven and the pressure to implement it came not from concerned regional CMS officials but from external pressures likely arising from persons or groups who stand to benefit financially from slowing down Provenge's pathway to becoming the standard of care for prostate cancer. Financially conflicted and well connected oncologists whose careers, clinical trials, investments and ego were strongly aligned with competing drugs to Provenge were able to pressure the FDA into delaying the approval of Provenge in May 2007. Even at the FDA Advisory Panel, one of these doctors was quoted directly and unequivocally as saying that he was concerned Provenge would quickly become the standard of care for prostate cancer treatment. These very same forces were likely at work behind the scenes in this NCD process as well.

Congressional investigation of this FDA decision was sought by many leaders in Congress back in 2007, and now again, the prostate cancer community can only hope that in this case as well, Congressional oversight can dig underneath the veneer to understand why CMS leadership abused the application of the NCD process with Provenge. Perhaps justice will be served this time around.

N.B. CMS, please delete my previous comment since for some reason no paragraph spaces were inserted by your computer system, making it impossible to read.

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April 9, 2011

To: CAG, re Administrative File CAG-00422N

From: Joanne Lynn, MD, MA, MS, DrJoanneLynn@gmail.com

Re: Proposed National Coverage Determination for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer

I am writing to encourage the National Coverage Determination for Sipuleucil-T to be much more constrained than the current proposal envisions by making the following adjustments:

1. All of the potentially salient restrictions that applied to the three major studies of this treatment should be imposed upon the coverage, rather than the substantial generalization that the FDA adopted and that this proposed coverage rule would accept. Specifically, this would include:
   1. That the patient be able to come to a treatment center (implied)
   2. That the patient be capable of, and in fact provide, informed consent (implied)
   3. That the diagnosis and extent be documented, including disease progression
   4. That the PSA be >5.0 ng/mL
   5. That the testosterone level be < 50 ng/dL
   6. That the blood counts, creatinine, bilirubin, and hepatic enzymes be adequate as defined in the studies
   7. That the patient be tested and known not to have HIV, Hepatitis B or C, or Human T cell lymphotropic virus-1
   8. That the patient not have prostate cancer metastases to liver, lung, brain, ascites, or pleura
   9. That the patient have no pain requiring opioids, and no pain >4 on a scale of 10,
   10. That the patient have no disability greater than ECOG=>2 (that is, no ADL impairments, not in bed more than normal, and capable of all but strenuous physical activity)
   11. Various medications and chemotherapies cannot have been used within 6 months
   12. No pathologic fractures or high risk of same, no spinal cord compression
   13. No Paget’s disease, no other cancers, no immunosuppressive therapy
   14. No recent infection or fever
   15. No contraindication to contrast dye
   16. Prognosis to live more than 6 months
2. Medicare should ensure strong implementation of the requirement for patient co-pay for all eligible beneficiaries with substantial assets (not also on Medicaid) and should monitor the rate at which eligible patients decline the treatment and why.
3. Medicare should ensure strong implementation of the requirements for consent, including informing the patient of the modest gains to be expected, the expectation of rigors, the need for travel, the costs, and the other treatments possible (including palliative care without treatment aimed to alter the usually slow progression of asymptomatic and minimally symptomatic metastatic disease).
4. Medicare should require evidence development with all use of this treatment, whether under the covered “on label” use, the non-covered “on label” use, the potentially expanding labelling, and any “off label” use.

EFFECTIVENESS IS PROBABLY OVERSTATED. This is a very expensive treatment for a condition that mostly afflicts persons in advanced years, who also have many other problems. Indeed, the fact that the patients, even when carefully selected, had so many other conditions has complicated the attribution of effects (beneficial and adverse) in the studies to date. This treatment has been studied only in a few hundred affected people, and only in a small series of studies managed by researchers and the sponsoring pharmaceutical company. If this treatment follows the usual course, its effectiveness will turn out to be substantially attenuated in ordinary application.

PROPOSED COVERAGE GOES BEYOND EVIDENCE. The requirements for enrollment in the studies, as documented in the proposed coverage rule, were sufficiently limiting that only a minority of the persons who might be eligible (as having minimally symptomatic or asymptomatic metastatic hormone-resistant prostate cancer) would actually have qualified for the studies. Most actual patients would not have had sufficiently robust performance status, and many would not have been competent for consent. Considering the minimal requirements under the proposed overbroad coverage determination, the usual eligible patient may well be an elderly man with no trouble from a slow-growing prostate cancer, living with dementia and frailty (and usually six to ten major diagnoses), perhaps in a nursing home. This kind of patient was not part of the research cohort, and we simply do not have evidence on the question of the merits of this treatment in this sort of patient. Only the minority who would have been eligible for study should be covered at this time. Illnesses associated with frailty in the elderly affect the immune system profoundly, and one would expect that the merits of a immunologically-mediated treatment might well be much attenuated in a frail elderly person. Thus, this treatment should not be covered for a patient like this at this time.

CO-PAY SHOULD ROUTINELY BE COLLECTED. Since this is an outpatient treatment, the patient will be expected to pay 20%. Undoubtedly, this liability will weigh on insurance rates, and I am not clear as to whether supplemental Medicare insurance will be allowed to cover this treatment as a “rider” or in another way to signal to the purchaser the impact of coverage for this sort of low-benefit, high cost treatment. However, in the usual situation, co-pays routinely are not collected because the practitioner is allowed to make the determination that the patient is too poor (so long as the practitioner attempts to collect the co-pay for some reasonable array of patients). In the sipuleucil-T situation, it will be important to have patients really contribute to the costs, in part to see whether the very small expected benefit is worth even 20% of the cost. Thus, Medicare should provide surveillance to understand the rate of the treatment being offered and declined due to the co-pay cost, among patients who could have put together the nearly $20,000 that the co-pay costs. The most efficient way to do this might be to have an on-line form that the patient (or patient’s representative) would fill out, creating an immediate registry of all Medicare patients who were considered eligible and were offered the treatment.

DECISION TO USE THIS TREATMENT SHOULD MEET HIGH STANDARDS FOR UNDERSTANDING AND CONSENT. For parallel reasons, Medicare should ensure that the patients meet a high standard of decision-making. The data establishing benefit are marginal, and the practitioner is attending a person with a known but usually indolent disease that is causing no substantial symptoms and putting him through a treatment that incurs distressing rigors more than half of the time, as well as various other discomforts – in pursuit of a survival benefit that requires hundreds of subjects to detect. So the patient will not feel better for this treatment but might live a little longer, with various added symptoms and substantial personal and societal costs. It would be reasonable for a man in advanced years to turn this down just to avoid the annoyance, and it certainly would be reasonable for him to turn it down from the cost (to himself or to the society generally). So, CMS and the involved clinicians should develop a standard set of materials for teaching and for testing, to be sure that patients had the opportunity to make this decision themselves, with good information, and not to simply go along with the preferences of providers. That information should be available in various formats and languages to meet the needs of a variety of beneficiaries and families. Again, an on-line interview might be required in order to document understanding and voluntary choice (which could now be documented on video at very little added cost or burden).

USE IN MEDICARE BENEFICIARIES SHOULD DEVELOP ADDITIONAL EVIDENCE. Finally, CMS should require that a minimum data set be kept on every Medicare patient considered eligible for sipuleucel-T treatment, and perhaps for such a registry to be made available to all patients regardless of payment source. This would assure high compliance with the requirements above for coverage, co-pay, and consent, and the data would provide an ongoing monitor of the actual effectiveness in persons with various characteristics. Potentially, these data could be managed in cancer registries or in a data registry managed by a grant to an academic institution, perhaps funded jointly by the manufacturer, CMS, and NIH.

SUMMARY. In short, the coverage determination proposed for sipuleucel-T is overbroad and inadequately tailored to provide the foundation for good decisions about this and other similarly high-cost, low yield treatments in the future. Under current law, CMS probably must cover this treatment for persons who are quite similar to those studied, but CMS should carefully limit coverage to the areas with evidence and not generalize the coverage so broadly, and CMS should act to ensure that we continue to generate the information we will need to manage this and similar treatments in the future, including evidence as to the patients’ preferences and values.

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Extremely happy for the men in my family and the country now that such an advancement in medical science will be available going forward.

Probably one of the most significant medical break-throughs to arrive on the scene in years. The data supporting Provenge's effectiveness is such a clear hit especially in light of the fact that Provenge had to compete with itself for much of the survival curves highlighted in the Ph III trials as a good portion of the placebo group for humanitarian reasons were allowed to switch over to Frovenge, a frozen, less potent version of Provenge.

By the very nature of how Provenge works, training/stimulating the bodies immune system to recognize and attack PC, it stands to reason that we may inveritably have a cure if this treatment were moved up further in the treatment line. Those that participated in the Ph III trial were terminally ill, had wrecked immune systems from PC and poisonous chemo treatments. Provenge potentially could wipe out PC in an individual with a healthy immune system to stimulate.

Provenge has unbelievably minor side effects relative to chemo. These lack of side effects outside of flu like symptoms brings the aggregate cost of Provenge down when compared with chemo as there are no incremental costs associated with "treating the symptoms of the treatment".

Finally, the platform upon which Provenge works has far reaching potential and may be applicable to many other forms of cancer.

Bravo on the decision to recommend this treatment as medically necessary.

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Thank you for the positive determination that Provenge is a reasonable and necessary treatment for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer.

I would also like to implore CMS to start a NCD to reverse the coverage of Taxotere in the on-label Provenge patient population as a first-line therapy. Only if Provenge has been administered or an Oncologist/Urologist deems it necessary should the US taxpayer be burdened with Taxotere since it is now proven to be an inferior treatment for asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. Out with the old, in with the new.

Thank you for allowing us to comment.

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I am very encouraged by your draft National Coverage Determination Letter regarding coverage of the label indications for Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer also known as Provenge. Provenge provides a needed alternative to chemotherapy in treatment of their disease.

I have a friend who is battling prostate cancer at this time. The availability of Provenge may be too late in coming for him. But it will provide a welcome tool in a fight for additional quantity and quality of life for many men.

It is encouraging that you have left future coverage of off label (or earlier) treatment to the discretion of the medicare contractors. I am confident that data collected by medicare will demonstrate that earlier usage by patients who are reacting poorly to hormone ablation treatment may very well save the medicare system money in the long run.

So, please, I encourage you to proceed with the issuance of the final NCD in the same form as the draft as soon as possible.

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Dear Sir/Madame: I'm a retired army officer and a New York attorney. I invest in ground breaking bio-technology and the future of our great nation. I shall only comment briefly on the need for CMS to provide coverage for Provenge.

The evidence is overwhelming that Provenge is safe and effective for the treatment of advanced prostate cancer. The FDA has approved the use of Provenge for the treatment of men with advanced prostate cancer.

Provenge has a clearly established survival advantage compared to chemo-therapy. And the side effects from treatment with Provenge are limited to flu like symptoms. This is compared to the devastating and crippling side effects of chemo that often results in extensive hospitalization or death.

Therefore, Provenge is "reasonable and necessary" within the meaning of the law, and there is no basis for CMS to deny covergage. So the remaining issue, in my judgment, is why CMS initiated a NCA for Provenge when it has no legal discretion regarding coverage?

I believe the answer is sad and simple. CMS is simply another captured federal agency responding to special interests. In this case, I believe CMS officials initiated the NCA on behalf of hedge funds which had shorted the stock of Dendreon.

CMS officials have never before initiated a NCA under similar circumstances. CMS officials knew the share price of DNDN would plummet if they initiated a NCA. CMS explanations regarding its decision to initiate a NCA for Provenge are wholly unpersuasive.

Is it any wonder the citizenry of our great nation have lost confidence in our federal government? In its determination to initiate a NCA for Provenge, CMS officials have brought great discredit upon themselves and their agency, and further tarnished the image of our federal government.

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I applaud the FDA for their belated approval of Dendreon's groundbreaking cancer immunotherapy, Provenge.
Provenge (sipuleucel-T)was approved by the FDA in early Spring 2010 to treat men with Hormone Refractory Prostate Cancer. The trial data revealed a median survival advantage of a robust 4.1 months.

In the long history of cancer research, no cancer treatment other than Provenge, has such mild side-effects, e.g. flu-like symptoms lasting @2-3 days, of which, only some Provenge patients experience. No other medicine beyond Provenge for HRPC has a survival advantage of 4 months and which exhibit such a favorable side-effect /quality of life profile as Provenge.(Only 3 other cancer drugs have been shown to increase survival by more than 4 months in the past 20 years.) Provenge stands alone at the top of all cancer treatments with respect to its benign side-effect profile.

Comparing median survival benefits between Provenge and Taxotere shows Provenge@ 4.1 months (side effects: Fevers and chills for a few days. Symptoms treated with aspirin.) vs. Taxotere @ 2.4 months median survival (hair loss, allergic reaction, fainting, nausea... may need hospitalization)

Comparing treatment the costs:

Provenge: $93,000 ONCE per lifetime.

Taxotere: Up to $54,000, not counting further costs to treat side effects.

Provenge’s median survival benefit exceeds other cancer drugs. In fact, at 4.1 months, it is nearly twice as long as that of Taxotere, the current standard of care for the same disease indication, HRPC. And, that survival benefit is obtained with minimal side effects, meaning improved QOL for patients than when Taxot

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I would like to see at a minimum the proposed decision be adopted as it covers what the Trial targets have targetted, while leaving the door open for coverage of earlier use. Common sense would say that a treatment that trains the immune system would have increasing effect (and lower lifetime overall medical expense) the earlier it is used. Thus unlike standard chemo, Provenge has both a medical and an overall cost benefit; I urge CMS to allow early use to be covered.

I also have a criticism: the time delay of ~1 year in getting to an NCD is egregious. This needs to be improved to 3 months max; ideally would be done concurrent with the approval process itself so all is handled upon approval.

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Initial public opinions submitted to CMS were overwhelmingly positive for Medicare to cover Provenge. During CMS meeting, expert testimonies were provided and again, overwhelmingly positive to cover Provenge. The CMS panel votes were consistent with the public opinion/experts and were overwhelmingly positive.

Made complete sense that CMS' March 30 release to cover Provenge was consistent with public opinion, expert testimonies and CMS panel votes. I support a final CMS decision to be consistent with its March 30 release for Medicare to cover Provenge.

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My family has a history of dealing with prostate cancer. I believe Provenge has the potential to become the new standard of care for prostate cancer.

Using England's National Institute for Clinical and Health Excellence, or NICE criteria for cost-effectiveness, the ANNUAL COST of Taxotere+side-effects cost is approximately equal to the LIFETIME COST of Provenge + side-effects.

Every effort should be made to make Provenge an available and accessible option for prostate cancer patients.

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As a healthcare advocate and senior(70+)it seems to me that overall benefits to the health of senior citizens would be enhanced greatly by approving the process of autologous cellular immunotherapy for prostate cancer.

I concur with Representative John Conyers(D-Michigan)in his letter to recent Cancer Institute committee that most cancer research in the last twenty years has not accomplished intended goals of direction, commitment and cooperation of these various organizations to stamp out these diseases.

Please encourage the efforts of Dendreon to seek innovative therapies in treatments of many cancers. I ask you in your ruling in June to encourage innovations that seem to come from private companies such as Dendreon who are achieving goals aimed at benefiting healthcare in America.

Thank you for your effort in protecting the best healthcare in the world.

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Dear CMS,

I hope your final determination will be in support of Provenge at least for "on label" use I feel Provenge should be the standard of care for patients with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer.

Your decision regarding "off-label" use was fair. You could have proposed national non-coverage of off-label use but didn't.

There is an argument in logic that Provenge will works even better at an earlier stage of prostate cancer. I would certainly want to try...after all, with the lowest side effect profile of any of the approved treatments for early stage and the likelihood my quality of life would be protected, what would I have to lose.

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I welcome the draft decision by CMS that deems use of Provenge as "reasonable and necessary."

Treatment of cancer needs newer technologies and Provenge represents an important first step in that direction. To harness the body's own immune system to fight cancer is an important paradigm shift. There exists the possibility that early use of Provenge may provide even better benefits for prostate cancer patients. Without approval and widespread use of Provenge, we may never know the true potential and the benefit that Immunotherapy can bring for cancer patients.

Provenge has mild side effects compared to Chemotherapy and quality of life is significantly better. The overall costs are even comparable when one takes into account costs associated with possible hopitalization from Chemo use.

From an economic perspective, Provenge is not any more expensive than current total cost of Chemo. Moreover, compared to Chemo with median survival of 2 months, Provenge at median of 4.1 months is scientifically superior. Put differently, the 40% increase in survival compared to placebo makes Provenge a true Gold Standard in treating Prostate cancer.

Unfortunately, cancer has affected many families (including mine) and we hope that Immunotherapy will provide one more meaningful way to help cancer patients. Thank you for the opportunity to comment.

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Dear Sir/Madam

It is fantastic that CMS is recommending reimbursement for Provenge treatment. In my opinion, as a research scientist of over 30 years, with current emphasis in oncology drug discovery, I view Provenge as a breakthrough paradigm in cancer treatment. It's superior efficacy and benign side-effects profile over the current standard of care, Taxotere, is dramatic, and incredibly encouraging when one considers the advanced stage of the study population. I look forward to a formal endorsement of Provenge on June 30th. Anything less would be a serious setback for humankind.

Sincerely
Ciaran N Cronin PhD.

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Provenge took over ten years to development and for late stage Prostate Cancer patients it has proven to extend life with minimal side affects compared to chemotherapy.
Given the fact that immunotherapy works best when given early I humble request that the FDA and CMS allow a wide birth and favorable label requirements to allow experimental usage in earlier stages of Prostate cancer. Earlier usage will allow Doctors to uncover all the potential that Provenge has to offer. The side effects are minimal but the potential upside is enormous.

Provenge represents a new way to treat cancer and with better a understanding of earlier usage might help other drugs like Nuevenge get to market quicker.

Very few drugs have shown the promise that Provenge offers and that cost has been in the Billions. So before we spend another Billion trying to find the next Provenge lets use a fraction of that amount to find out what Provenge can do. I request that Provenge be reimbursed in some off label cases so that Doctors can unlock everything that Provenge has to offer.

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Provenge is the new standard of care.

A first in kind treatment - PC patients are truly fortunate to have this option.

It is time to draw a line under this unnecessary debate.

The results presented to the FDA were indisputable and approval was given.

Immunotherapy is the future for cancer treatment and a true way forward to lessen the burden on healthcare through the expensive costs of treating the horrendous side effects of cheno-therapy.

The treatment of prostate cancer with Provenge is only the first cancer that will be better served and managed through harnesing the bodys immune system.

Draw a line under this debate now!

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I would like to congratulate CMS for their draft decision in providing coverage for Provenge. Provenge is a significant scientific breakthrough in cancer treatment based on years of research and clinical studies where overall survival is clearly demonstrated.

Men with advanced prostrate cancer can now have a better option than chemotherapy. This approval will paved the way for more treatment options in the future.

Thank you again and I look forward to the final decision in June.

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I am president of Care To Live, the not for profit organization that fought long and hard, along with the Abigail Alliance, for the approval of Provenge.

Now that we have met our goal, and Provenge is FINALLY approved, it is so very important that we encourage treatment with Provenge, as it is a major shift in the way cancer is attacked. Instead of losing the war, we finally have a chance of "winning", by utilizing this smarter, safer, more sensible way to attack the enemy.

Anybody who knows anything about how the body works, understands the importance our white blood cells play in fighting off disease. Once this barrier is broken, and cancer begins destroying our immune system, Provenge sends in stronger white cells (an oversimplification) to assist our cells in fighting the cancers. Some men are living as long as 10 years after the three infusion regiment.

The past standard of care for late stage prostate cancer is to destroy a person's entire immune system, healthy and diseased cells alike, in order to destroy the cancerous cells. This leaves the body in a weakened state to fight for survival. Not only weakened, but often in a much sicker state than before the treatment.

Many people never recover from these toxic, extremely expensive chemotherapeutic treatments. Post treatment horrible side effects after chemotherapy are also subjected to additional expensive treatments, just to try to manage them, often unsuccessfully.

Care To Live is extremely pleased with your recommendation that Provenge be included for national coverage.

Thank you for the transparency you have displayed in regards to this process.

Sincerely,

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Dear Sir or Madam:

I am glad that you are recommending reimbursement for “on label” use of Provenge.

Please consider partial reimbursement for “off label” earlier use. It is important that you get involved with immunotherapy at earlier stages of disease to verify that, as many Doctors have suggested, immunotherapy should work even better the sooner it is given.

By offering partial reimbursement to earlier users and requiring follow-up for life, you can determine if, in fact, it would be beneficial and cost effective to use immunotherapies sooner than in the very sickest patients it is currently allowed for.

Thank you,

Karl Schreiber

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It is a huge advancement in the medical community and the cancer treatment sector to allow national reimbursement for Provenge.

This vaccine provides a revolutionary approach to the treatment of cancer and has been withheld from widespread public use for a shamefully long period of time. We are discussing the number two killer of men from cancer in the United States.

Provenge is a proven treatment which not only extends life expectancy but provides a quality of life that is much higher than that afforded by the chemotherapy alternative.

I am confident too, as more data is compiled that Provenge will be shown to have value in treating men with early stages of disease than is currently considered on-label usage.

DISCLOSURE: I am an investor in the company that manufactures and sells Provenge. I am a physician that treats the complications that men with advanced prostate cancer have to deal with including the horrendous life-draining effects of chemo. I always put patient needs before personal investing goals.

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The decision to fully support and allow CMS coverage/reimbursement for Sipuleucel-T (aka Provenge) used for FDA approved on-label indications is the correct one in my opinion.

In the short term, the cost of Provenge when one looks at the overall picture is actually less than Chemotherapy treatments (Taxotere) for Prostate cancer because of the number of Chemo treatments needed and other medical costs due to the bad side effects of Chemotherapy. Provenge also is a much more effective treatment which has only mild flu-like symptom side effects and it allows patients on average a 40% greater chance of surviving 3+ years vs. a Placebo.

In the long term, Provenge being a Immunotherapeutic type treatment has an opportunity to lower medical costs for the U.S. and provide a great solution to one of humanities worse diseases, cancer. As more and more early stage patients of Prostate cancer receive Provenge for Prostate cancer it's benefit has the potential to be greatly increased due to stronger immune systems of these patient groups and to not allow the cancer to progress to late stages which would limit the financial strain caused from treating late stage patients with traditional methods.

Again, I fully agree with the CMS's decision to support reimbursement for Provenge for FDA on-label indications. And although I would have seen the same support for off-label indications (early stage of the disease which Provenge may have a more profound effect due to stronger immune systems of these types of patients) I am encouraged that the CMS draft is open to allowing this down the line with further medical/trial data.

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To: Louis B. Jacques, MD
Director, Coverage and Analysis Group

Tamara Syrek Jensen, JD
Deputy Director, Coverage and Analysis Group

James Rollins, MD, MSHA, PhD.
Director, Division of Items and Devices

Leslye K. Fitterman, Ph.D.
Lead Analyst and Epidemiologist, Division of Items and Devices

Lori Paserchia, MD
Medical Officer, Division of Medical and Surgical Services

Eileen Pencek, RN, BSN, MBA
Analyst, Division of Medical and Surgical Services

I was impressed with your proposed decision memorandum (PDM). All the evidence is in, you show your understanding of it, and I will not waste space going over that. Unfortunately, the need and utility of NCD/NCA(?) set against the backdrop of denied coverage, uncertainty of coverage, and the least of concerns, unnecessarily diminished share-holder value due to unnecessary uncertainty and of course, the factor of wasted time which allowed rotten to the core entities to profit from this unnecessary process, is highly questionable.

However, this process as laid out in this PDM, in the end is reassuring; maybe a restoring of faith in Government to some degree has occurred here, I will try to explain. Never has there been less trust of Government than at this time, at least there is a high degree of mistrust. That said, your (CMS’) PDM— in its totality but with special regard to the off-label “proposed decision” numbers 2 through 4, to actually promote the individual Mac’s to cover off-label as they deem appropriate in every individual case as evidence develops— is stunningly smart, caring and un-bureaucratically productive, imo:

2. Autologous cellular immunotherapy is a new paradigm in the treatment of cancer, and we do not yet know if the development of additional evidence will follow the same trajectory as manufactured pharmaceutical products. Should the pace of evidence development for these products prove to be faster-paced and indicative of improved health outcomes, we believe that preserving local contractors’ ability to quickly broaden coverage within their jurisdictions will hasten beneficiary access.

3. The Provenge regimen, in contrast to a manufactured pharmaceutical, is based on the auto-transfusion of the patient’s own treated white blood cells. We believe this regimen may evolve over time, whereas with manufactured pharmaceutical products the therapeutic entity itself remains constant. The potency of the administered preparation itself is unique from patient to patient and may even differ in a given patient from administration to administration. If future evidence demonstrates improvement in patient health outcomes as a result of incremental improvement(s) to the current labeled process, we want our administrative contractors to have the flexibility to determine local coverage without the need to reconsider an NCD.

4. Similarly, should future evidence demonstrate improvement in patient health outcomes for populations not meeting the current labeled indication, we want our administrative contractors to have the flexibility to determine local coverage without the need to reconsider an NCD.

However, below is the first in that section and the only part of that section I can never agree with in as much as this action as evidenced by the development of the present NCD is extremely detrimental to Patients and their Families, Caregivers, manufacturing and Shareholders who are citizens and taxpayers. The unusual nature of the present NCD, coupled with the ease of fraudulent misuse of “anybody can cause an NCD” at the expense and with the abhorrent mal-use of patients in an extortion, is very bureaucratic, non-caring and unwise, when other quiet, non-disruptive remedies can be employed. Maybe picking up the phone and contacting an individual Mac site who might be at odds with your determination to clear up any abuse- rather than holding the manufacturer and Pc patients and families, not to mention all the various investors, hostage and responsible for insurance issues- would be a better path. Much better than actually helping miscreants waiting in the wings to cause or take advantage of those situations.

1. The manufacturer has acknowledged at the MEDCAC that there is no persuasive evidence to support unlabeled uses at this time. Thus we are hopeful that unlabeled uses in the near future will take place only in the context of bona fide clinical studies. We may, if this turns out to be an overly optimistic viewpoint, reconsider this NCD to ensure that Medicare coverage is restricted to uses that are supported by robust evidence.

With the above described concerns in mind, I am happy to support and am wishful for an immediate implementation of your PDM in the hour that follows this public comment period, or even before!

Sincerely,
David Paladin

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i strongly urge you to give full approval to provenge. this drug represents the currently available maximum effect balanced by the minimum negative efect in the treatment of prostate cancer. the cost of the medication is not only within the range of similarly priced chemotherapeutic treatments, but represents a comparatively lower cost due to the extremely limited supportive care needed to mitigate side effects. provene is, indeed, a reasonable and necessary weapon in the armamentarium of prostate cancer treatment.

thank you.

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I applaud the Centers for Medicare and Medicaid Services for their draft decision to cover Dendreon's Provenge. This is the beginning of a new age of cancer care that will provide patients with more effective, more humane, and more affordable treatments.

Media confusion about the cost of the treatment and its effectiveness is discouraging. Only three treatments in the last two decades have extended life to this degree.

Arguments that claim that Provenge is too costly, ignore the cost of chemotherapy which frequently entails recurring infusions, hospitalization, and ameliorating medications used to treat the toxic side-effects.

By approving Provenge coverage, CMS has provided hope for a better future to many cancer patients. Thank you.

Sincerely,

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I’m sure in the end we’ll all benefit from these small steps taken by companies like DNDN. I know it cost them billions to get this approved.

However it is beyond my belief that this treatment is going to cost the tax payers $93,000 and only prolong life for +/- 4 months. In my opinion the end doesn’t justify the means here. This voodoo witchery needs to stop.

It is time for Mr. Public to confront the inevitable that eventually we all are going to die. We shouldn’t have to drain the coffers in our efforts to stay alive for an extra week or even 16 weeks and we should be watching out for those who are going to end up footing the bills that our government is pilling up with these costly new treatments.

I know it’s a tough choice to make therefore maybe a compromise from both DNDN and our government to give companies like DNDN some type of tax relief or guarantee to allow DNDN over a longer period of time to recoup their losses in exchange for a more reasonable price would be a happy outcome for everyone, especially our children who will have to foot the bill after we are all long gone. Medicare is a branch of our government and should have the power to demand a better deal for the tax payers while at the same time making sure that companies like DNDN who did pass the FDA hurdles to stay in business.

I feel that Medicare should negotiate a better deal than to continue to dish out our tax money on these new treatments. Both parties should do what is best for those needing this treatment and come to a compromise.

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Doctors against Provenge reimbursement are not fully informed.
Legally Medicare must cover treatments for the Medicare population that are "reasonable and necessary". There can rationally be no questioning whether Provenge is reasonable and necessary for men with late stage prostate cancer. It is a true breakthrough in cancer treatment—harnessing the patient's immune system to fight the cancer, while producing very minimal side effects. Provenge has produced the greatest survival benefit EVER for this disease, and the results have been heralded in the New England Journal of Medicine and the treatment has been accepted by the NCCN as first line treatment for the indication. While I have noted that some commenters have emphasized the "slight" benefit at 4.1 months median life extension and the "high" cost, I would point out that those who make these comments have in fact been misled by the rather shallow media coverage of Provenge. While it is true that the median benefit was 4.1 months in the Impact study, later analysis by Duke Medical Center researchers has suggested that the study design—which compared Provenge to later given salvage Frozen Provenge—actually may have resulted in understating the treatment's benefit because it seems the frozen salvage product itself extended life. Indeed, the New England Journal of Medicine article on Provenge itself noted that the Provenge treatment group actually enjoyed a 14.2 month median survival advantage over the control group members who did not receive frozen Provenge and thus were "pure placebo". In any event, since by definition of "median" half the studied men lived more than an extra 4.1 months, a much more telling measure is the three year survival rate. The three year survival rate for men treated with Provenge improved by a whopping 40%. It should also be noted that Medicare has already determined, correctly, to cover the only other life extending treatment for this indication—Taxotere—and Taxotere extends life only by a median of 2.6 months and is much harder on the patient, producing classic chemo side effects, which can even include death. As to cost, Provenge is not "$93,000 per year", as many commenters have stated based upon erroneous press reports, but $93,000 for a one time full course of treatment. Again to compare to Taxotere, the prices are comparable when one factors in the necessity for multiple courses of treatment for Tax and the cost of treating and controlling the side effects. And, of course, Medicare may not legally consider price in the first place in making its statutory determination of "reasonable and necessary".

Morally there is likewise no question coverage is the right decision. These men deserve every chance to live extra years—and Provenge DOES provide every man who gets it the chance to live extra years. I need not discuss "death panels" and whether Big Brother should be denying elderly men a chance to see their grandchildren, because in spite of the media hype over healthcare reform that is stirring many commenters to make negative comments I know that the decision memo was produced in the spirit of the enabling Act, which guarantees these men every available chance to live without regard to cost. Still, financially the decision is also the right one and my only complaint is that it does not go far enough. As I have said, the cost of Provenge is fully in line with comparable cancer treatments. Where I disagree with the memo financially—and legally for that matter— is in its failure to cover off label use. Money and more importantly lives would be saved, I believe, by covering Provenge use in earlier stage disease. The Impact results were obtained in the sickest possible prostate cancer population, in men whose immune systems were already severely compromised. And still Provenge extended lives. There is every reason to expect that Provenge in earlier stage disease, in men with stronger immune systems, will work even better, save more lives, save more money. The researchers themselves have even expressed publicly the hope that in earlier stage disease Provenge will prove to be a cure. I believe that Medicare coverage off label would allow this hypothesis to be tested out much more quickly in the real world. I do praise the memo for at least not denying off label usage nationally and allowing local determinations to be made as to off label coverage.

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CMS - You have made the most appropriate decision possible with regards to both scientific standards and moral standards.

You'll read many a comments from people who lament about the pricing of Provenge. Please continue to see through these comments for what they are. They are simply investors who tried to bet against your review.

Anyone with a knowledge of the science, a loved one who has suffered from cancer, or any compassion at all understands the need for Provenge to be approved and paid for my Medicare.

This is a MEDIAN survival of 4.1 months. Meaning half of the Provenge population lived longer then 4.1 months many of them living for years. I believe $93,000 is a small price to pay for giving people the potential for years of additional "pain free" life. Please remember that approving payment of Provenge allows patients who suffer from staring at death in the face from having to also be the recipient of terrible side effects shown with many other treatments.

Most importantly being able to potentially avoid chemotherapy. Something that causes hair loss, appetite loss, extreme fatigue, damage to the body immune system, and in some cases death. It's poison and all told with the medications needed to counteract the side effects of Chemo you are looking at paying upwards of $93,000 regardless.

As for off-label use. Kudos for leaving this discussion open. As it's rather clear that the longer the body has an opportunity to allow Provenge to works its process, the better the chances of survival. And as Dendreon is given the opportunity by CMS to prove such, you could very well have made the decision of sponsoring with your payments the future cure or stabalizer for prostate cancer.

All the negatives are from investors who bought the wrong side of the Dendreon trade. Not from scientists, not from patients, and certainly not from the loved ones of those who have seen people afflicted with this disease.

Thank you again for doing what was scientifically and morally the right thing to do.

Regards,

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To CMS,

I want to thanks CMS for voting to reimburse for Provenge. By this action you have opened the door on research into immunotherapy's for other forms of cancer. We are now assured that there will indeed be a new treatment paradigm that is beginning to take the place of the cut, burn and poison as new insights into cancer immunotherapy are learned.

What better treatment can be had than to have a treatment that teaches our own immune system to recognize cancer cells as foreign and kill only them. We now have the first treatment to do just that in Provenge.

I can't understand the wisdom of people who would not want this new era in cancer treatment to move forward and who are favor of keeping the old style less effective treatments that are as costly and less user friendly.

I can't understand the statement I just read, that people should be taught how to die with dignity when I believe we should be learning how to live life to the fullest...all of it...!

Provenge is the first real breakthrough in the war on cancer, declared by Richard Nixen, over decades ago.

Soon there will be immunotherapy's for other forms of cancer.

But first, Provenge had to happen.

Humanity will be the beneficiary of this new form of treatment.

Thank you for allowing me to express my feelings on this matter.

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I am commenting in response to the excellent decision by CMS regarding Dendreon's Provenge. Provenge has produced the greatest survival benefit ever for this disease, and the results have been reported in the New England Journal of Medicine. Since by definition of "median" half the studied men lived more than an extra 4.1 months, a much more telling measure is the three year survival rate. The three year survival rate for men treated with Provenge improved by a whopping 40%. It should also be noted that Medicare has already determined, correctly, to cover the only other life extending treatment for this indication—Taxotere—and Taxotere extends life only by a median of 2.6 months and side effects are much more harsh than Provenge. Provenge is not "$93,000 per year", as many commenters have stated based upon erroneous press reports, but $93,000 for a one time full course of treatment. Again to compare to Taxotere, the prices are comparable when one factors in the necessity for multiple courses of treatment for Tax and the cost of treating and controlling the side effects. And, of course, Medicare may not legally consider price in the first place in making its statutory determination of "reasonable and necessary". Financially the decision is also the right one and my only complaint is that it does not go far enough. There is every reason to expect that Provenge in earlier stage disease, in men with stronger immune systems, will work even better, save more lives, save more money. The researchers themselves have even expressed publicly the hope that in earlier stage disease Provenge will prove to be a cure. I believe that Medicare coverage off label would allow this hypothesis to be tested out much more quickly in the real world. Please cover Provenge for both on label and off label usage. This is the first step of changing cancer treatment and may indeed be the first step to a cancer cure one day. Both on and off label reimbursement will change lives for many, many years and be well worth the investment. CMS has the decision in their hands to help take those first steps. Please make the right decision and cover both on and off label reimbursement of Dendreon's Provenge.

Thank you.

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I am commenting to state my total support for the CMS decision to cover Provenge for men with late stage prostate cancer. There is absolutely no question that this is the correct decision—legally, morally, financially—by every relevant measure.

Legally Medicare must cover treatments for the Medicare population that are "reasonable and necessary". There can rationally be no questioning whether Provenge is reasonable and necessary for men with late stage prostate cancer. It is a true breakthrough in cancer treatment—harnessing the patient's immune system to fight the cancer, while producing very minimal side effects. Provenge has produced the greatest survival benefit EVER for this disease, and the results have been heralded in the New England Journal of Medicine and the treatment has been accepted by the NCCN as first line treatment for the indication. While I have noted that some commenters have emphasized the "slight" benefit at 4.1 months median life extension and the "high" cost, I would point out that those who make these comments have in fact been misled by the rather shallow media coverage of Provenge. While it is true that the median benefit was 4.1 months in the Impact study, later analysis by Duke Medical Center researchers has suggested that the study design—which compared Provenge to later given salvage Frozen Provenge—actually may have resulted in understating the treatment's benefit because it seems the frozen salvage product itself extended life. Indeed, the New England Journal of Medicine article on Provenge itself noted that the Provenge treatment group actually enjoyed a 14.2 month median survival advantage over the control group members who did not receive frozen Provenge and thus were "pure placebo". In any event, since by definition of "median" half the studied men lived more than an extra 4.1 months, a much more telling measure is the three year survival rate. The three year survival rate for men treated with Provenge improved by a whopping 40%. It should also be noted that Medicare has already determined, correctly, to cover the only other life extending treatment for this indication—Taxotere—and Taxotere extends life only by a median of 2.6 months and is much harder on the patient, producing classic chemo side effects, which can even include death. As to cost, Provenge is not "$93,000 per year", as many commenters have stated based upon erroneous press reports, but $93,000 for a one time full course of treatment. Again to compare to Taxotere, the prices are comparable when one factors in the necessity for multiple courses of treatment for Tax and the cost of treating and controlling the side effects. And, of course, Medicare may not legally consider price in the first place in making its statutory determination of "reasonable and necessary".

Morally there is likewise no question coverage is the right decision. These men deserve every chance to live extra years—and Provenge DOES provide every man who gets it the chance to live extra years. I need not discuss "death panels" and whether Big Brother should be denying elderly men a chance to see their grandchildren, because in spite of the media hype over healthcare reform that is stirring many commenters to make negative comments I know that the decision memo was produced in the spirit of the enabling Act, which guarantees these men every available chance to live without regard to cost.

Still, financially the decision is also the right one and my only complaint is that it does not go far enough. As I have said, the cost of Provenge is fully in line with comparable cancer treatments. Where I disagree with the memo financially—and legally for that matter— is in its failure to cover off label use. Money and more importantly lives would be saved, I believe, by covering Provenge use in earlier stage disease. The Impact results were obtained in the sickest possible prostate cancer population, in men whose immune systems were already severely compromised. And still Provenge extended lives. There is every reason to expect that Provenge in earlier stage disease, in men with stronger immune systems, will work even better, save more lives, save more money. The researchers themselves have even expressed publicly the hope that in earlier stage disease Provenge will prove to be a cure. I believe that Medicare coverage off label would allow this hypothesis to be tested out much more quickly in the real world. I do praise the memo for at least not denying off label usage nationally and allowing local determinations to be made as to off label coverage.

In sum I urge CMS to implement the draft memo as its final decision in June.

Excellent work!

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This therapy, which is not a drug, signals a new approach to treating cancer patients. In clinical trials it has shown significant survival results over placebo and standard of care Tx.

A 40% increase in 3 year survival is only one of the results. It should also be remembered that the trial group, because of ethical considerations, was comprised of only very sick patients. Meaning, that more work needs to be done with a healthier trial group to see if the effects of Provenge are even greater when used on healthier subjects.

The cost of 10+ years of development is very very high. New approaches do not come along every day. In fact, this is the first in immunotherapy approved by the FDA. I hope that the lives of male patients will receive the same valuation as is extended to women in our society.

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I cannot begin to describe my visceral reaction to the news that Medicare is choosing to cover a $93,000 non-curative treatment that MAY exend life by 4 months. Given Medicare's actions in cutting reimbursement to physicians for proven, life prolonging testing and services (with a fraction of the cost) over the past few years, the decision is even more appalling.

As I go to work tomorrow at my medical practice, worried about our financial solvency because of Medicare's recent actions and cuts, this decision will be hard to forget. Perhaps other phyhsicians will benefit from this in the long run as well...the patients will survive a bit longer for more unnecessary testing, procedures, and medications that Medicare can pay for as well.

Medicare should be a leader in helping physicians and patients deal with end of life care and issues. This is not something to be ashamed of, and I consider this an extremely important part of my job as a physician. Decisions like this by Medicare give patients false hope and unrealistic expectations, but keeps Medicare leaders from being criticized by uninformed political leaders on the evening news who believe helping a patient pass with dignity is the same as 'rationing care'.

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Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (sipuleucel-T)

I am a board certified urologist, practicing in private practice since 1981, now retired.

I have followed the sipuleucel-T testing. In my opinion, this is not an effective and certainly not cost effective treatment option for prostate cancer. there is sparse objective data with no psa benefit, the outcome of a three month survivial benefit is not truley clinically helpful to an endstage dying paitnet, and the costs are certainly very high.

I believe the treatment approval should be reconsidered. There should be independent testing by others than those finacially involved with the treatment.

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