Gilead Sciences, Inc announced phase-II clinical trial results showing that its investigational fixed-dose single-tablet "Quad" regimen of elvitegravir, GS 9350 (cobicistat) and Truvada (emtricitabine and tenofovir disoproxil fumarate) for the treatment of HIV infection exhibited antiretroviral activity comparable to thatofAtripla) (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg). At 24 weeks, the proportion of patients who achieved HIV RNA (viral load) less than 50 copies/mL was 90 percent in the Quad arm and 83 percent in the Atripla arm (using an analysis where missing equals failure, intent-to-treat population). Discontinuation rates due to adverse events were comparable in both arms of the study. These data will be presented today at the 17th Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco (Abstract #58LB).
"Simplified treatment regimens of co-formulated, fixed-dose medicines have become the standard of care in HIV therapy because they can help patients adhere to dosing schedules," said Calvin J Cohen, principal investigator and director of Research, Community Research Initiative of New England. "These positive efficacy and safety results indicate that the Quad has the potential to become an important new treatment option in HIV therapy."
The Quad contains four Gilead compounds in a single, once-daily tablet: elvitegravir, an investigational integrase inhibitor for HIV; cobicistat, a pharmacoenhancing or "boosting" agent that increases blood levels of certain HIV medicines; and Truvada, which is itself a combination of the two HIV medicines emtricitabine and tenofovir disoproxil fumarate.
Gilead is also studying cobicistat as a stand-alone boosting agent for other antiretroviral medications - in particular, once-daily protease inhibitors such as atazanavir. Currently, ritonavir is the only agent used to boost HIV therapy. Data from a phase-II clinical trial evaluating the safety and efficacy of cobicistat-boosted atazanavir plus Truvada compared to ritonavir-boosted atazanavir plus Truvada will also be presentedtoday at CROI.
"We are dedicated to developing new HIV treatment regimens that feature improved efficacy and tolerability profiles, both of which are increasingly important as patients remain on therapy for longer periods of time," said Norbert W Bischofberger, Gilead's executive vice president, Research and Development and Chief Scientific Officer. "We are excited about these results and look forward to working with the US Food and Drug Administration to finalize the phase-III clinical program for the Quad and cobicistat."
Elvitegravir is an HIV integrase inhibitor. Unlike other classes of antiretroviral agents, integrase inhibitors interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells. Elvitegravir was licensed by Gilead from Japan Tobacco Inc. (JT) in March 2005. Under the terms of Gilead's agreement with JT, Gilead has exclusive rights to develop and commercialize elvitegravir in all countries of the world, excluding Japan, where JT retains rights.
Cobicistat (formerly GS 9350) is Gilead's proprietary potent mechanism-based inhibitor of cytochrome P450 3A (CYP3A), an enzyme that metabolizes drugs in the body. In addition to studying the agent as part of an integrase-based fixed-dose regimen, Gilead is also examining cobicistat's potential stand-alone role in boosting commercially available HIV protease inhibitors, which are used in many HIV treatment regimens.