Autologous Blood Derived Products for Chronic Non-Healing Wounds

January 18, 2008

VIA E-MAIL AND FEDERAL EXPRESS

Beverly A. Lofton, MHA
Lead Analyst
Centers for Medicare & Medicaid Services
7500 Security Blvd.
Woodlawn, MD 21244
Mail Stop: C1-09-06

Re: Comments on Proposed Decision Memo for Autologous Blood-Derived Products for Chronic Non-Healing Wounds (CAG-00190R2)

Dear Ms. Lofton:

On behalf of Organogenesis Inc., I respectfully submit these comments regarding the Centers for Medicare & Medicaid Services’ (“CMS”) Proposed Decision Memo for Autologous Blood-Derived Products for Chronic Non-Healing Wounds (“Proposed Decision”). Organogenesis agrees with the Proposed Decision and its conclusion that the evidence is not adequate to determine that autologous platelet-rich plasma (“PRP”) is reasonable and necessary for the treatment of chronic, cutaneous wounds. As set forth in more detail below, we urge CMS to issue a final non-coverage determination for the use of all PRP gel products in the treatment of chronic, cutaneous wounds because (1) the clinical evidence fails to demonstrate their effectiveness in healing diabetic foot ulcers, venous stasis ulcers, or pressure ulcers and (2) there are no standardized procedures for processing and applying PRP gel to such chronic wounds. A non-coverage determination for PRP would help ensure that Medicare beneficiaries suffering from chronic wounds do not receive inappropriate and medically unnecessary treatments and procedures.

THE CLINICAL EVIDENCE CMS REVIEWED FOR ITS PROPOSED DECISION FAILS TO DEMONSTRATE THAT PRP GEL IS MEDICALLY NECESSARY FOR HEALING CHRONIC, CUTANEOUS WOUNDS

A U.S. Food and Drug Administration (“FDA”) guidance document, entitled “Guidance for Industry, Chronic Cutaneous Ulcer and Burn Wounds – Developing Products for Treatment” (“FDA Guidance”), provides guidelines for sponsors designing clinical trials on products intended to treat chronic, cutaneous ulcers and burns. While CMS certainly is not required to adopt the clinical trial guidelines discussed in the FDA Guidance, given the wide range of products currently marketed for wound management or wound healing and the varying levels of clinical data to support their efficacy and safety, the clinical recommendations in the FDA Guidance afford CMS with a benchmark for evaluating each product and its intended use.

The FDA Guidance suggests certain factors that sponsors should consider, including randomization and stratification, comparator arms, blinding, wound assessment and quantification, and study population, when designing wound-healing clinical trials. It also recommends that sponsors conduct separate clinical trials for each intended use because ulcers differ in pathophysiology, and the results obtained in a trial for one ulcer type cannot be generalized to another ulcer type.

We agree that the seven studies submitted in support of coverage for PRP gel for healing chronic wounds have multiple flaws, many of which CMS highlighted in the Proposed Decision. We discussed many of these deficiencies in our previous comment letters, which are attached as Appendix A. We highlight the following:

We have been using "AutoloGel" PRP to treat wounds at Kindred Hospital Oklahoma City since April of 2002. This procedure has provided dramatic wound healing results with 30 to 40% wound size reduction, "healing", within the first 10 to 14 days. This indirectly has provided a wound treament savings of $500 to $750 per week, and provided shorter lengths of stay for our wound patients. Patient satisfaction is high, because most patient''s come to us with history of wounds that have been treated for months to even years without resolution or improvement. There is no question as to whether this procedure works, it is just a matter of getting the patient ready and the wound in a healthy clean condition to start application of the "AutoloGel" procedure. This procedure provides results, patient satisfaction and a dramatic cost savings. Kindred Oklahoma City has been treating at least 40-50 patients per year. The cost of approximently $300 per week vs use of a VAC at $500 to $750 per week. Regular wound dressings using enzymes, zeno grafts and/or alografs which can run $300 to $1,800 per week is very expensive and time consumeming, but also with less quality results. When using this procedure, just be ready for the productive and positive results.

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I have been utilizing platelet gel on procedures for approximately nine years and have one published paper,double blinded, prospective, IRB approved study: Autologous Platelet Gel Applications During Cardiovascular Surgery Effect on Wound Healing, Susan J. Englert, Thomas H. Estep, Cynthia C. Ellis-Stoll, JECT. 2005; 37:148-152. I have another paper pending publication in JECT; Retrospective Study of Postoperative Surgical Chest and Leg Incisions Utilizing Autologous Platelet Gel. Please contact me for futher questions.

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Dear Sirs,
While I am not a titled medical professional, I would like to add a comment on your proposed decision regarding Autologel. The data submitted by Cytomedix for Autologel specifically was randomized, propsective, double blinded and controlled patient trials. This appears to be the benchmark in the medical industry. CMS has provided coverage for wound care treatments previously that had no such data in support. These include Vacuum Assisted Closure and Hyperbaric Oxygen treatments. CMS has provided reimbursement for wound care products previously that have this supporting data but are products with much lower efficacy outcomes. It seems inconsistent that the FDA would provide clearance of Autologel, in fact, giving a specific indication for wound healing but yet CMS would deny coverage to those that cannot afford the treatment other than on a "private pay" basis. The testimony provided in this public comment section shows that wound care professionals are enjoying remarkable success using Autologel. Quality of life for many patients has improved as their wounds are healed. The costs associated with lingering chronic wounds have diminished as the wounds have been closed. The trial data showed evidenced in Cytomedix'' patient trials demonstrated healing rates above 80% for wounds treated. Given the FDA clearance and these noted outcomes, why would those patients dependent on Medicaid/Medicare be excluded or denied access to the benefits enjoyed by private pay patients?

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I have been involved in PRP usage for 13 years. In that time I have witnessed great healing from the use of PRP in Chronic non healing wounds.

I will not understand how it can not seen in the best interest of patients to at least allow some coverage for the use of prp. This could be a coverage for the use of it as a last resort. It has been use this way without coverage and wonderful results have been seen. I have had patients request prp as a last resort and before amputation of a limb and the reusults have been no lost of the limb.The question is on what papers d0 you base your desicion on. There are some papers out there that state that prp does not work these papers generally do not state the concentration of the PRP. If the concentration is not six times higher that base line there probably be no benefit to the wound.

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I have seen wonderful results with the autologel therapy. I had limited experience in the actual procedure of the treatment until a few weeks ago when a wound care physican at my facility asked if the facility could provide the treatment. The facility was in the process of hiring a CEO and so I had to go through corporate to get the go ahead. "The corporate CEO said if this order goes to waste I will put it at your feet to pay for. My mentor in wound care once told me a truth i will never forget." If you do the right thing at the right time for the right reasons you will get good results. The Autologel Therapy has met this criteria. The Autologel therapy has priven its worth by the acellrated healing we are seeing with its use.

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My name is Leon Gurvich, I''m ANP and CWS and have great opportunity to use Autologous Blood Derived Products for Chronic Non-Healing Wounds for the last 3 years during my work in Wound Healing Center in L.Weiss Memorial hospital, Chicago, IL. I have very good experience with this product with miracle results in some patients. This product is very helpful in healing wound with tunneling and undermining. We call this product “Biological glue” for the tissue. Studies in basic science have shown a dose-response relationship between the platelet concentration and levels of secretary proteins, as well as between platelet concentration and certain proliferative events of significance to the healing wound . The platelet is a natural source of a myriad of growth factors and cytokines that promote wound healing. Platelet-derived angiogenesis factor is a polypeptide capable of stimulating new capillary growth by inducing migration of endothelial cells. Platelet-derived epithelial cell growth factor is partially responsible for the initial influx of neutrophils into the wound space; it is also a mitogen for many cells, including epithelial cells and fibroblasts.

We have done about 25-30 patients treated with Autologel with good response and NO side effects or any complaints from the patients. We would like to continue using this product and hope that CMS will approve it and find the way for reimbursement.

Sincerely, L.Gurvich.

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Sirs......I am a ICU nurse with 25 years experience...have seen many different types of wounds and treatment regimes. Recently I was able to assist in PRP treatment of an elderly lady with a chronic wound on her ankle. She had this wound for several months and standard..wet to dry gressing, etc..were not effective in healing this wound. After the very first treatment...significant difference was noted in the wound...and she was thrilled!! Follow up treatments have significantly improved the wound and she is very happy with the results. Dana J. Walker RN

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I am most disappointed in your decision not to cover Autogel for use in patients with chronic wounds. I am one of few phyiscians in the US who practices full time chronic wound care. I have used Autogel for years with outstanding results.

I have used it primarily in the LTACH setting where the wounds are typically larger and much worse than in the outpatient clinic. I have used it on all types of wounds that have failed to respond to conservative treatment, namely venous leg ulcers, Diabetic foot ulcers, pressure ulcers and traumatic ulcers. In almost every instance the wounds have improved and the great majority have gone on to heal. Without doubt the treatment has reduced hospital stays and thus has been a money saver for payees.

In addition the treatment has no safety issues since the patient "receives" his own blood products that go on his own wound.

I strongly urge you to reverse your decision not to cover Autologel. It works and the data does and will continue to show that it does work. Chronic wound patients desperately need products that work, since many of the hundreds on the market do not perform as advertised.

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Respectfully, issuing a blanket denial of reimbursement coverage for ALL platelet gel wound healing products is overkill. As a matter of public policy, any FDA-approved product shown to work in randomized, double-blinded clinical trials should NEVER be denied the opportunity for possible reimbursement, even with conditions attached. This is especially the case here, where the chronic wound patient endures extreme hardship and suffering, and far too frequently amputation or even death, should the wound not heal promptly.

As such, respectfully, I propose that CMS carve out from its non-coverage determination those autologous platelet gel systems that:

(I) are FDA-approved, with indications for use in the treatment of chronic, non-healing wounds; and

(II) are supported by randomized, blinded clinical trials having statistically significant results favoring the system’s ability to improve the rate of wound closure in patients with chronic, non-healing wounds.

Such limitations close the floodgates to potential waste and abuse, yet provide physicians and patients with a safe, clinically effective way of attacking the chronic wound scourge; a scourge that lacks a “magic bullet” that an FDA-approved,trial-tested autologous platelet gel system could well provide (and that my own eyes have personally witnessed) and that also costs taxpayers billions annually.

Applying this logic to your analysis of chronic,non-healing wounds at Section VIII of your draft decision yields the conclusion that the AutoloGelSystem – the only autologous platelet gel system that is both FDA approved and supported by successful clinical trial results – should not be barred per se from coverage. Rather, consistent with your analysis, CMS should carve out from its non-coverage determination those autologous PRPsystems – like AutoloGel – that bbeen approvednapproved by the FDA and havepositive resultsveresults in a "prospectively costudy designudydesign.” For while the AutoloGel clinical trial may not, in your words, “conclusively demonstrate the ability of [the whole universe of] autologous PRP to improve the rate of wound closure inpatients with chronic, non-healing wounds,” it does “conclusively demonstrate the ability of autologous PRP [derived via the AutoloGel System]to improve the rate of wound closure in patients with chronic, non-healing wounds.” (Bracketed language inserted by commenter.)

Finally, your analysis at Section VIII notes that “prospectively controlled study designs” (such as the AutoloGel trial) “can lead to the generation of robust evidence by limiting bias and confounding.” Given this truism, as long as such a study design yields statistically significant results, why should it matter (particularly given what’s at stake here in terms of patient suffering and taxpayer cost) that statistically significant results in the AutoloGel trial were winnowed from the data and not part of the original hypothesistested? Total wound closure rates of 81% (p-valueof 0.036) were achieved among AutoloGel-treated patients in wounds of 7 sq. cm. and less (representing the vast majority of chronic wounds treated today). That these wound-healing results were determined by analysis of the data and were not the originally tested hypothesis should not detract from the validity of the conclusions reached (and thus similarly should not detract from that system''s ability to qualify for reimbursement coverage).

Thank you for your thoughtful consideration of mycomment.

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