Merck, Gilead Release Strong Findings From Clinical Trials of Experimental Integrase Inhibitor Antiretroviral Drugs

Whitehouse Station, N.J.-based Merck and Foster City, Calif.-based Gilead Sciences on Wednesday at the 13th Conference on Retroviruses and Opportunistic Infections in Denver reported "surprisingly strong" findings from clinical trials of their experimental integrase inhibitor antiretroviral drugs, the San Francisco Chronicle reports (Russell, San Francisco Chronicle, 2/9). Integrase is one of the three enzymes necessary for HIV to replicate in the body, and integrase inhibitors would stop HIV from inserting its genes into normal DNA. The other two enzymes necessary for viral replication -- reverse transcriptase and protease -- already are targeted by a variety of antiretroviral drugs (Kaiser Daily HIV/AIDS Report, 7/9/02). According to the Wall Street Journal, both experimental drugs appear to be effective in HIV-positive patients who are resistant to other treatments (Chase, Wall Street Journal, 2/9). Merck -- in a clinical trial involving 167 patients who had a multiple-drug-resistant virus and a history of unsuccessful treatments -- compared a combination of antiretroviral drugs with its integrase inhibitor MK-0518 or a placebo. Researchers gave all patient groups antiretroviral drugs, but one group received a placebo and the other groups received MK-0518 at different dosages over the 16 week study period. The antiretroviral drugs and MK-0518 combination reduced HIV viral loads to undetectable levels 72% of the time in the most responsive dosage group and 56% of the time in the less responsive dosage group, the company reported (San Francisco Chronicle, 2/9). According to the Journal, the group taking a combination of antiretroviral drugs and a placebo had viral levels drop 19%. The Gilead trial, which tested the company's integrase inhibitor GS-9137 in 30 HIV-positive patients for 10 days, found that the patients had as much as a 99% decrease in viral loads compared with a group of 10 patients taking a placebo who had a smaller reduction in their viral loads, the company reported (Wall Street Journal, 2/9). Gilead's study also found that its drug was safe for patients over the 10-day period, the Chronicle reports.

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"The search for integrase inhibitors has been a long one,' Warner Greene -- director of the Gladstone Institute of Virology and Immunology in San Francisco, who had no role in the Merck study -- said, adding, "We've said all along that you need to attack this virus in multiple parts of its life cycle. The third viral enzyme has been elusive, but the barrier seems to be cleared' (San Francisco Chronicle, 2/9). Merck and Gilead are planning to start larger clinical trials that test the efficacy of the experimental treatments later this year. Pending the results of the trials, Merck said the company has plans to apply for FDA approval in 2007 (Wall Street Journal, 2/9).

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