New Antiretroviral Fuzeon Benefits HIV-Positive Patients With Drug Resistance to Other Antiretrovirals, NEJM Studies Show
The new antiretroviral Fuzeon, also known as enfuvirtide or T-20, doubles the chances that an HIV-positive patient who has developed resistance to existing drugs can achieve undetectable blood levels of the virus, according to two studies published in today's issue of the New England Journal of Medicine, the Miami Herald reports. The FDA and the European Union have already approved Fuzeon, which was jointly developed by drug makers Roche and Trimeris, even though clinical trials of the drug were not yet complete. The drug, the first in a new class of drugs called fusion inhibitors, works by preventing HIV from entering healthy cells. Calling Fuzeon's approval "very important," Dr. Corklin Steinhart, medical director of the Florida AIDS Education Training Center in Miami, said, "This is the first drug to be specifically approved for people who have run through the usual HIV medications, and who don't have a lot of other options to help keep the virus under control." However, a complex, 106-step manufacturing process means that the drug will not be widely available, and it is expensive, costing up to $20,000 per patient per year. Susan Pisano, spokesperson for the American Association of Health Plans, said that health insurance companies will likely cover the cost of the drug. "What I'm hearing suggests that the real question won't be coverage by private insurers," she said, adding, "It will be availability" (Tasker, Miami Herald, 5/29). Roche will only be able to produce enough of the drug to treat fewer than 10,000 patients in the United States, according to ABCNEWS.com (McKenzie, ABCNEWS.com, 5/28). The following is a summary of the studies, as well as two other HIV-related articles published in today's NEJM:
- "Enfuvirtide, an HIV-1 Fusion Inhibitor, for Drug-Resistant HIV Infection in North and South America": The FDA's decision to approve Fuzeon prompted NEJM to release the results of this study in March. Researchers studied approximately 1,000 participants from 48 cites in the United States, Canada, Mexico and Brazil who had at least six months of previous treatment with three classes of antiretrovirals. The study, called the T-20 vs. Optimized Regimen Only Study 1 (TORO 1), concluded that adding enfuvirtide to an existing 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, 5/29).
- "Efficacy of Enfuvirtide in Patients Infected with Drug Resistant HIV-1 in Europe and Australia": Sixty-seven researchers studied almost 1,000 participants from France, Spain, Italy, Germany, Australia, the United Kingdom, Belgium, Switzerland, the Netherlands and Sweden. Participants had to have been treated with at least one antiretroviral from each of the three approved classes of drugs for at least three months prior to entering the study. The study, called the T-20 vs. Optimized Regimen Only Study 2 (TORO 2), found that adding enfuvirtide to an existing antiretroviral regimen "provided significant viral suppression and immunologic benefit over a 24-week period" in participants who had previously received multiple antiretroviral drugs and who had multi-drug resistant HIV (Lazzarin et al., NEJM, 5/29).
- "Fusion Inhibition -- A Major but Costly Step Forward in the Treatment of HIV-1": Drs. Karen Tashima and Charles Carpenter of Miriam Hospital in Providence, R.I., write in an accompanying editorial that the studies of enfuvirtide offer "heartening news of the success" of the drug. The studies used almost identical methodology, and it is "most encouraging that the studies yielded nearly identical results," they write. Still, as the drug becomes more widely used, several issues will have to be considered, they say. For example, if an HIV/AIDS patient develops resistance to the other drugs in the regimen, viral resistance to enfuvirtide will develop "rapidly," Tashima and Carpenter say. In addition, the drug's cost is almost double that of the next most expensive antiretroviral drug. Another "major concern" is the potentially serious toxic side effects linked to the drug, the editorial continues. While these issues "are important, they should not detract from the welcome demonstration of the effectiveness of this HIV-1 fusion inhibitor, the first successful inhibitor of viral entry," Tashima and Carpenter conclude (Tashima/Carpenter, NEJM, 5/29).
- "HIV Infection -- A New Drug and New Costs": Enfuvirtide is "noteworthy" because it works differently than previous antiretrovirals and "heralds an era of new approaches to treatment," Dr. Robert Steinbrook writes in a NEJM perspective piece. He says that the drug is "very expensive" and should therefore be considered a "prototype product that should lead to the development of less expensive medications of the same general class," but it is unknown how long that process will take. In addition, safety is also a "concern" because almost all patients who take enfuvirtide, which is administered twice a day by injection, have at least one injection-site reaction. Also, it will be difficult to make the drug "on a scale large enough to provide sufficient supply for tens of thousands of patients," Steinbrook says. He calls for further study of the drug in longer periods of treatment to "establish the durability of the response" found in other drug studies. Steinbrook concludes, "Antiretroviral therapy can be improved through many approaches, including the development of new classes of drugs, better drugs with fewer side effects, and more convenient dosing for existing classes of drugs. Enfuvirtide may eventually be replaced by a simpler drug with fewer side effects that can be taken by mouth or injected less frequently than twice a day" (Steinbrook, NEJM, 5/29).
- "Novel Therapies Based on Mechanisms of HIV-1 Cell Entry": Dr. J. Kilby from the University of Alabama-Birmingham Department of Medicine, and Dr. Joseph Eron from the University of North Carolina-Chapel Hill Department of Medicine, offer an "outline [of] the steps involved in viral attachment" and cell entry, provide an update on "agents under development that have been designed to inhibit each of these steps, and consider the prospects of these compounds in the treatment of HIV." According to Kilby and Eron, "Targeting viral entry may have advantages over the inhibition of steps in the viral life cycle after the cell has been infected. A better understanding of how HIV-1 binds to and enters cells has prompted a reappraisal of previous attempts to block viral entry and an evaluation of new approaches" (Kilby/Eron, NEJM, 5/29).
PRI's "Marketplace Morning Report" today reported on the NEJM studies of Fuzeon. The segment includes comments from study co-author Dr. Calvin Cohen (Parrella, "Marketplace Morning Report," PRI, 5/29). The segment will be available online in RealPlayer after the broadcast. This is part of the KHN Morning Briefing, a summary of health policy coverage from major news organizations. Sign up for an email subscription.