FDA Panel Supports Approval of Boehringer’s Aptivus To Treat Drug-Resistant HIV, Requests Additional Data
An FDA advisory panel on Thursday "cautiously" supported Boehringer Ingelheim's protease inhibitor Aptivus in combination with Abbott Laboratories' Norvir for use by HIV/AIDS patients who have become resistant to other drugs, Reuters reports. The panel voted 11-3 to back the drug for use in the United States but also called for more data from long-term studies into Aptivus' effects on the liver and cholesterol levels (Heavey, Reuters, 5/20). FDA, which will consider Aptivus -- known generically as tipranavir -- under its accelerated review system, is expected to make a decision on the drug by June 22.
Boehringer presented the panel with data from two "key" clinical trials showing that HIV-positive patients who received Aptivus in combination with Norvir "responded better" than patients treated with a combination of different antiretroviral drugs, according to the Wall Street Journal. Many patients in the two trials had become resistant to about 12 other antiretroviral drugs (Corbett Dooren/Whalen, Wall Street Journal, 5/20). In one trial, about 40% of participants who received Aptivus and a low dose of Norvir reduced their viral loads after 24 weeks, compared with 21% of patients who received Abbott's Kaletra. A second study showed that 13% of patients who took Aptivus and Norvir "showed improvement," compared with 9% of participants who took Norvir with another protease inhibitor, Drug Industry Daily reports (Drug Industry Daily, 5/19). The panel also noted that when the antiretroviral drug Fuzeon -- which is made by pharmaceutical companies Roche and Trimeris -- was added to the Aptivus/Norvir combination, the "treatment effect was even more significantly greater than if (Fuzeon) was not used" (Wall Street Journal, 5/20).
Safety Concerns, Additional Information
Although most panel members said that Aptivus was effective, they expressed concern about the drug's long-term effects on the liver and cholesterol levels, according to Reuters. A previous study indicated initial liver toxicity in healthy people taking the drug, and a subsequent long-term trial showed that 10% of participants taking Aptivus experienced liver complications, compared with 3% of participants taking similar antiretroviral drugs, according to FDA staff (Reuters, 5/20). Panel members and FDA also said they are concerned about the drug's possible interactions with some commonly used medications, such as those to treat diabetes and high cholesterol. They also expressed concern about an increased incidence of rashes among female trial participants, who comprised only 15% of patients in the clinical studies, according to the Journal (Wall Street Journal, 5/20). The panel therefore recommended that Boehringer conduct more long-term studies on possible liver problems associated with the drug and its effects on women and minorities. Panel members also said that Boehringer should ensure that doctors are aware of Aptivus' risks. Boehringer has said it also is conducting studies to test the drug in HIV-positive children and adults who have not developed drug resistance. Peter Piliero, Boehringer's senior associate director of virology, said that studying the drug in treatment-naïve HIV-positive people also would help the company to understand how long it takes patients to develop resistance to Aptivus. He added that the company is tracking study participants for up to five years because it is "concerned about the toxicity issues" (Reuters, 5/20).
Although the panel expressed safety concerns about Aptivus, it said there is a "great need" for new treatments for HIV/AIDS patients who are not responding to other drugs, the Journal reports. "We feel the need for this drug in this patient population is high and the risks are certainly present," Janet Englund, an infectious disease expert at Children's Hospital and Medical Center in Seattle and chair of the FDA panel, said (Wall Street Journal, 5/20). She added, "I think everyone is concerned that patients involved in these studies ... need longer-term follow up." Douglas Fish, a nonvoting panel member and professor at Albany Medical College, said the risks associated with the drug are "manageable" and they are the "kinds of complications, especially in these highly pretreated populations, that have become a reality of HIV care in 2005" (Reuters, 5/20). According to Charlie Hicks, an HIV researcher at the Duke University Medical Center who helped conduct the Aptivus clinical trials, the drug is the "most significant protease inhibitor to come before the FDA in several years," the Journal reports (Wall Street Journal, 5/20). However, Maribel Rodriguez-Torre, a physician in Puerto Rico and panel member who voted against approval, said, "I understand the need. I'm concerned about so many drug interactions" (Reuters, 5/20).