FDA Approves Fuzeon, First in New Class of AIDS Drugs

The FDA yesterday approved Fuzeon, an antiretroviral drug designed for HIV/AIDS patients who have failed to respond to other medications and the first drug in seven years that uses a new method to fight the virus, the Washington Post reports (Brown, Washington Post, 3/14). The FDA approved the drug for use in combination with other antiretroviral medications to treat advanced HIV infection in adults and children ages six years and older (FDA release, 3/13). Unlike the three other classes of HIV treatments -- nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors -- which all attack the virus after it enters the cell, Fuzeon is in a new class of drugs called fusion inhibitors, which prevent the virus from entering cells by prohibiting the virus from attaching to cell membranes (Washington Post, 3/14). Fuzeon's approval was processed through the FDA's accelerated approval mechanism and was based on an analysis of six months of data from two ongoing clinical trials of the drug involving about 1,000 patients (FDA release, 3/13). Almost all of the patients who take the drug, which is injected twice a day, experience local skin reactions at the injection site, including "painful nodules" that form underneath the skin (Russell, San Francisco Chronicle, 3/14). The FDA warned that patients must be careful to prevent skin infections at the injection site. Fuzeon can also cause "serious systemic allergic reactions," including breathing problems, fever, skin rash, chills, vomiting and low blood pressure, according to the FDA. The approved labeling for Fuzeon also warns doctors to monitor patients for signs and symptoms of pneumonia. Although bacterial pneumonia was uncommon in clinical trial participants, more patients taking Fuzeon experienced the infection than patients who were not taking the drug (FDA release, 3/13). The FDA's decision prompted the New England Journal of Medicine to release a study of the drug originally set for publication on May 29 (Agence France-Presse, 3/14). The study, called the T-20 vs. Optimized Regimen Only Study 1 (TORO 1), concluded that adding Fuzeon to an existing "optimized" antiretroviral regimen "provided significant antiretroviral and immunologic benefit through 24 weeks" in participants who had previously received multiple antiretroviral drugs and who had multi-drug resistant HIV (Lalezari et al., NEJM, 3/13).

Getting The Drug To Patients
Trimeris, the biotech company that developed the drug, and Roche, the Swiss pharmaceutical company producing and marketing the drug, expect to begin shipping Fuzeon by late March or early April (Kaiser Daily HIV/AIDS Report, 3/13). Including patients already involved in clinical trials and an early access program, the companies predict that approximately 3,500 people will be on the drug by the end of this month, Reuters reports (Shields, Reuters, 3/14). Due to the complex 106-step manufacturing process required to produce the drug, Roche and Trimeris project that they will be able to supply the drug to between 12,000 and 15,000 patients this year and to approximately 32,000 by the end of 2004 (Ranii, Raleigh News & Observer, 3/14). About 10,000 of the patients receiving the drug in the first year of production will be in the United States, with the remaining patients in other countries (Washington Post, 3/14). The companies expect to get European Union approval for the drug in April or May, according to a Roche spokesperson (Reuters, 3/14). Between 20,000 and 100,000 HIV-positive patients in the United States are estimated to be candidates for the drug, so initial demand is expected to outstrip supply. In response, Roche has developed an allocation system wherein the drug will be distributed from a central pharmacy on a "first-come, first-served" basis. Physicians wishing to prescribe the drug to more than one patient will be asked to rank the patients in order of need (Washington Post, 3/14). "We have consulted a number of stakeholders: physicians, consultants, patient activists. We want to make sure the process makes sense," Heather Van Ness, a Roche spokesperson, said (Brand, Denver Rocky Mountain News, 3/14). Roche officials said that the drug is not suitable for use in Africa due to its high price, the complexity of the production process and the fact that most African patients have not yet developed resistance to existing drugs (Reuters, 3/14).

Pricing Concerns
Although Roche officials say that they will not disclose the U.S. price of Fuzeon until closer to its launch date, they say that it will fall within the range of the drug's price in Europe, which the company announced last month is about $20,514 per patient per year. Many AIDS advocates consider that to be a prohibitively high price for the drug, but the companies say that the drug's complex manufacturing process is to blame (Fuhrmans, Wall Street Journal, 3/14). The European price is almost triple the cost of the most expensive antiretrovirals on the U.S. market, and AIDS advocates fear that the additional $14,000 a year that it would add to traditional combination drug therapy may be prohibitive for low-income patients. Budget deficits have led to cuts in Medicaid, which pays for about 50% of all AIDS-related drugs, and federal- and state-funded AIDS Drug Assistance Programs, which pay for about 30% of the drugs (Kaiser Daily HIV/AIDS Report, 3/13). AIDS advocates yesterday set up a mock graveyard in front of Roche's U.S. headquarters in New Jersey to protest the drug's price (Washington Post, 3/14). The price "will hasten the death of thousands of people with HIV," Mark Milano of ACT UP, an HIV/AIDS activist group, said (Silverman, Newark Star-Ledger, 3/14). Next week, six of the biggest ADAPs will meet with Roche to discuss Fuzeon discounts. In addition, the company said that it plans to "contract independent reimbursement consultants" in order to help secure financial assistance for patients on Fuzeon (Wall Street Journal, 3/14).

Hope, Inspiration, Frustration
HHS Secretary Tommy Thompson said, "The accelerated approval of this new drug should provide new hope for those suffering from advanced HIV infection" (Denver Rocky Mountain News, 3/14). "Fuzeon adds an important dimension to our armamentarium of anti-HIV treatments. By affecting viral spread in a different way from existing medications, it helps reduce viral loads, which has been shown to slow HIV progression in patients who have developed resistance to currently available medications," FDA Commissioner Mark McClellan said (FDA release, 3/13). Experts predict that Fuzeon's approval will "drive significant new research," the AP/Atlanta Journal-Constitution reports. "It will not only help patients but [also] stimulate research in developing new classes of drugs," Debra Birnkrant, director of the FDA's division of antiviral drug products, said (Meckler, AP/Atlanta Journal-Constitution, 3/14). "I think it's a big deal. Anytime you have a new class of HIV drugs, it's a big deal," Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, said (Washington Post, 3/14). However, Martin Delaney, founding director of Project Inform, an AIDS advocacy group in San Francisco, said that he would consider the drug's approval "a much bigger deal if it were more affordable," the News & Observer reports. "There is no guarantee that people will be able to get it," he said, adding, "In fact, it is almost a certainty that some people won't be able to get it" because of the high price (Raleigh News & Observer, 3/14). Michael Montgomery, who oversees California's ADAP program, said, "We don't think we can add Fuzeon (to our drug list) without cutting something else. We are excited about the drug, but we aren't sure we can afford it." Matt Sharp of the AIDS Treatment Activists Coalition in Chicago added, "If Roche cannot get people to buy the drug through the ADAP program ... they are not going to have a market for the product" (San Francisco Chronicle, 3/14).

"NPR News" today reported on the FDA approval of Fuzeon (Knox, "NPR News," NPR, 3/14). The full segment is available online in RealPlayer.