Quad Pill Works as Well as Atazanavir Combo at 48 Weeks

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The experimental Quad pill -- a once-daily single-tablet regimen containing the integrase inhibitor elvitegravir, the novel boosting agent cobicistat, and the NRTIs tenofovir and emtricitabine -- met a 48-week primary endpoint demonstrating non-inferiority to a boosted atazanavir regimen, Gilead Sciences announced this week. Both combinations suppressed HIV RNA in about 90% of treatment-naive HIV patients, but fewer people discontinued the Quad due to side effects.

The Quad pill previously was shown to work as well as the Atripla single-tablet regimen (efavirenz/tenofovir/emtricitabine). Based on these promising Phase 3 data, the company has indicated that it plans to submit the new combo for U.S. Food and Drug Administration (FDA) review in late 2011 rather than early 2012.

Below is an edited excerpt from a Gilead press release describing the latest study findings.

Gilead's Second Pivotal Phase 3 Clinical Study of the Investigational Antiretroviral Quad Regimen Meets 48-Week Primary Objective

Foster City, Calif. -- September 19, 2011 -- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the second pivotal Phase 3 clinical trial (Study 103) of its investigational fixed-dose, single-tablet "Quad" regimen of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate, being evaluated for HIV-1 infection in treatment-naive patients, met its primary objective of non-inferiority at week 48 as compared to ritonavir-boosted atazanavir plus Truvada (emtricitabine/tenofovir disoproxil fumarate) based on the proportion of subjects who achieved HIV RNA levels (viral load) of less than 50 copies/mL.

The primary endpoint analysis indicated that 90 percent of patients in the Quad arm compared to 87 percent in the ritonavir-boosted atazanavir plus Truvada arm (95 percent CI for the difference: -1.9 percent to 7.8 percent) achieved HIV RNA of less than 50 copies/mL through week 48. The predefined criterion for non-inferiority was a lower bound of a two sided 95 percent CI of -12 percent. The discontinuation rate due to adverse events was higher in the ritonavir-boosted atazanavir arm (5.1 percent) as compared to the Quad (3.1 percent). This difference was driven primarily by elevated bilirubin levels observed in the ritonavir-boosted atazanavir arm. Other adverse events and laboratory abnormalities were similar between the two arms. Gilead plans to submit these data for presentation at a scientific conference early next year.

"The 90 percent response rate observed on the Quad arm in this study is an unprecedented result and speaks to the potency, safety and convenience of an integrase-based single-tablet regimen," said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. "Based on the availability of data from both pivotal Studies 102 and 103, we are now working toward filing for U.S. regulatory approval of the Quad by the end of the year."

About Study 103

Study 103 is a randomized, double-blind clinical trial comparing the efficacy, safety and tolerability of the Quad versus ritonavir-boosted atazanavir plus Truvada over a 96-week period at more than 200 study sites in North America, South America, Europe and Asia Pacific. Eligible participants are HIV-infected treatment-naive adults with HIV RNA levels greater than or equal to 5,000 copies/mL. Trial participants were randomized (1:1) to receive a once-daily tablet containing elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (n=353) or ritonavir 100 mg and atazanavir 300 mg plus Truvada (emtricitabine/tenofovir disoproxil fumarate) (n=355).

The primary endpoint of the study is the proportion of patients achieving HIV RNA levels of less than 50 copies/mL at 48 weeks of treatment. Secondary objectives will evaluate the efficacy, safety and tolerability of the treatment regimens through 96 weeks of treatment.

The study is ongoing in a blinded fashion. After week 96, subjects will continue to take their blinded study drug until treatment assignments have been unblinded, at which point all subjects will be given the option to participate in an open-label rollover extension and receive the Quad single-tablet regimen. Additional information about the study can be found at www.clinicaltrials.gov.

The Quad, elvitegravir and cobicistat are investigational products and have not yet been determined safe or efficacious in humans.

About the Quad

The Quad contains four Gilead compounds in a complete once-daily, single-tablet regimen: elvitegravir, an investigational integrase inhibitor; cobicistat, an investigational pharmacoenhancing or "boosting" agent that increases blood levels of certain HIV medicines; and Truvada. The Phase 3 clinical program for the Quad includes two studies (Studies 102 and 103) which are evaluating the Quad regimen versus a standard of care among HIV-1 infected antiretroviral treatment-naive adults. Study 102, a randomized, double-blind clinical trial comparing the efficacy, safety and tolerability of the Quad versus Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) is ongoing, and the company announced that the study met its primary objective of non-inferiority at week 48 on August 15, 2011.

About Elvitegravir

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.

About Cobicistat

Cobicistat 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.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.

For more information, please visit the company's website at www.gilead.com.

9/23/11

Source

Gilead Sciences. Gilead's Second Pivotal Phase 3 Clinical Study of the Investigational Antiretroviral Quad Regimen Meets 48-Week Primary Objective. Press release. September 19, 2011.