New-Fill on "Hold" and Open Label for T-20
Over the last several months countless numbers of HIV-positive individuals have had their spirits lifted, their morale boosted and their self-confidence improved. This was because a synthetic product called poly-lactic acid under the trademark New-Fill became available for personal use in the United States. New-Fill reversed many disfiguring facial abnormalities for many individuals; facial lipoatrophy changes are due in part to HIV drugs and HIV disease. Actually New-Fill has proved safe through clinical trials outside the U.S. and has been shown to be effective for HIV-positive individuals with facial lipoatrophy. As a result, many HIV-positive individuals sought out treatment through a limited number of centers that were approved to administer the product. The product's sale and use was administrated by DAAIR, a respectable buyers club based out of New York City. Further detailed background information regarding New-Fill can be found in my previous article from the September/October 2001 issue of Positively Aware and on the www.AIDSInfosource.com Web site.
After several months of smooth sailing with primarily trained plastic surgeons, almost by surprise, the FDA interceded and halted its use. A recent comment made by an unnamed HIV practitioner was "it appears that the FDA managed to find a loop hole 'vehicle' by which to interfere with personal wishes of individuals who suffer from the devastating facial side effects of antiretroviral therapy." Clearly it was the FDA themselves whose policy allows treatment for personal use, given that a drug is approved outside the U.S.
The October 26 action of the FDA halted all further distribution of New-Fill in the U.S.; therefore, the buying club DAAIR was in effect ordered to not release any more product for shipment -- this included shipping New-Fill to those who had already initiated treatment and were still in the process of having the 3-7 administrations needed for New-Fill to be completely effective. DAAIR is guardedly confident that it can fulfill all shipments of product for those patients previously initiated into treatment with New-Fill prior to October 26th; however, at this time they cannot ship product to anyone who would have started the procedures post 10/26/01.
The FDA decision was made by a small group of Directors within the FDA, from such areas as Personal Use and the Division of Compliance. The FDA based their decision to halt distribution of New-Fill on the technical terms of their guidelines of allowing availability. Originally, New-Fill was allowed to be accessed by PWAs under the "personal use guidelines." These guidelines permit use of drugs not yet approved here (but approved in other countries) and for the treatment of one of several qualifying illnesses determined by the FDA. Persons suffering from these illnesses (such as AIDS) can import a drug into the U.S. for their individual personal use. The FDA then decided, upon further examination, that since New-Fill required the expertise of a trained physician and/or plastic surgeon that it no longer should be considered a personal use drug. Moreover, the FDA maintains that as New-Fill does not remain in full control of the individual utilizing the product, it should be re-categorized as a medical device.
The FDA does not allow for medical devices to be imported for personal use -- all medical devices must be approved prior to use. The example the FDA gave was as follows: This situation would be similar to an artificial heart that was available in Europe but not yet approved for use in the U.S. The FDA would not allow anyone to import that artificial heart and subsequently would not authorize any surgeon to transplant said device -- if that individual wants to access that artificial heart they must travel to Europe and have the procedure done there. The FDA did acknowledge that they would consider a treatment-IND (Investigational New Drug) protocol for New-Fill (a clinical trial) -- however, this typically is itself a large administrative burden that can take minimally 3-6 months to complete and is usually done by the sponsoring pharmaceutical company.
Many medical specialists can state with confidence that New-Fill indeed is not a "device." Yes it requires someone to inject the product, but linking this to heart transplant surgery is quite a stretch. The product comes in a vial such as many other drugs and is simply reconstituted with sterile water or saline, like other drugs. It is drawn up in a syringe and injected. This does not require any sophisticated or mechanical devices or apparatus.
New-Fill has been approved for use in France and Mexico. Safety and effect studies performed satisfied the French requirements for approval. Additionally, several studies reported the use among HIV-positive individuals. Those reports were presented at the 2nd International Workshop on Adverse Reactions and Lipodystrophy in HIV in Toronto in September 2000 and the 8th European Conference on Clinical Aspects and Treatment of HIV Infection in October 2001 in Athens.
As mentioned, DAAIR remains guardedly confident that it can fill all necessary prescriptions for product to those that had initiated treatment prior to 10/26/01. DAAIR is looking at various avenues within FDA guidelines and is attempting further inspection of this issue. If the FDA's edict is left to stand, many affected persons will be wronged and deprived of a procedure that can potentially change their quality of life.
DAAIR is experiencing significant slow down and problems. During this writing, plans are being set up for a meeting with the FDA. In this meeting Martin Delaney of Project Inform, DAAIR management, and I with other interested parties will hope to clear up some of these issues. Additionally, clinical trials with New-Fill for a "lipoatrophy associated HIV disease" indication are on the discussion table. I will try to keep you all posted on the www.AIDSInfosource.com Web site as well as in further issues of my column in Positively Aware.
Trimeris and Roche teamed up to offer a new open label study for the administration of T-20 to the most needy of HIV positive patients. T-20 is a novel antiviral, first of a new class of fusion inhibitors (blocks fusion of HIV to CD4 T cells). This was not an expanded access program, but an open-label safety study and was severely limited to 168 patients nationwide.
The program was initially announced on 11/07/01 and details of the protocol and its operation posted on the Trimeris Web site. Additionally the companies announced that for "the letter distributed to doctors concerning the initiation of the study, visit the following Web sites: www.rocheusa.com or www.Trimeris.com." However as a physician who prescribes HIV medications, neither I nor the other physicians in our clinic have ever received such a letter. We have also spoken with several other community-based HIV physicians, none of whom received any letter.
The wire news story announced that a phone line would open at 3pm EST on November 27th for up to 56 physicians who would be allowed to sign up as investigators and enroll three patients each. The criteria for enrollment was CD4 T cell count <50 cells/mm3 and viral load >10,000. First preference would be given to those with a recent opportunistic event while on an anti-HIV regimen in the last 90 days. However, I attempted to get through by telephone to register, getting a busy signal and at times no response. I kept trying. Finally getting a recorded message that stated, "We're sorry, enrollment is now full." We were later told that the program closed in less than 20 minutes of opening.
Alex Dusek, Director of Marketing at Trimeris stated that this was their attempt to "serve the community in the most equitable manner" and "seeking the advice of many other people." As much as we appreciate the efforts of Trimeris and Roche to increase availability it remains that a majority of advanced patients were not served.
If these were Rolling Stones tickets that were on a first-come, first-serve basis, I could understand handling it this way. However, unfortunately the honest reality is that many individuals' lives are at stake. When protease inhibitors were in Phase III of development (1994) a lottery system of patient chart numbers was set up through physicians' offices and sponsoring pharmaceutical companies. Those programs provided a fair chance for all patients to receive drug. In contrast, the Trimeris/Roche program favored larger institutions that could afford to place a dedicated employee on the phone that day and dial as many times as needed to get connected. We were told that no comment can be made as to whether several institutions or sites enrolled more than one physician and potentially took up more than their share of very few spaces.
Mr. Dusek of Trimeris reiterated that a complicated manufacturing and production process limits supply. I encourage Trimeris to provide wider availability for patients with limited treatment options. During the recent years of development, T-20 access has been greatly restricted. I hope that without too many delays Trimeris and Roche will offer an expanded access program.
Daniel S. Berger, M.D. is Medical Director of Northstar Healthcare and Clinical Assistant Professor of Medicine at the University of Illinois at Chicago and editor of AIDSInfosource (www.AIDSInfosource.com). He also serves as medical consultant for Positively Aware. For further inquiries Dr. Berger can be reached at DSBergerMD@aol.com or (773) 296-2400.
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