Gilead Begins First Phase 3 Clinical Trials of Boosted Elvitegravir Quad Pill

Gilead Sciences announced this week that the first participants have started receiving therapy in Phase 3 trials of the "Quad" pill, a 4-in-1 coformulation containing the experimental integrase inhibitor elvitegravir, the new booster cobicistat (GS 9350), tenofovir, and emtricitabine. As reported recently at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010), the Quad pill performed as well as Atripla (the 3-in-1 efavirenz, tenofovir, and emtricitabine coformulation) in a head-to-head Phase 2 trial. The Phase 3 trials will compare the Quad pill versus efavirenz and boosted atazanavir (Reyataz) in treatment-naive patients.

Below is an excerpt from a Gilead press release describing the newly initiated Quad trials, as well as another Phase 3 study of cobicistat as a stand-alone boosting agent.

Gilead Initiates Phase III Clinical Program Evaluating
Single-Tablet, Once-Daily "Quad" Regimen for HIV

Foster City, Calif. -- April 12, 2010 -- Gilead Sciences, Inc. (Nasdaq:GILD) today announced that it has dosed the first patient in the Phase III clinical program evaluating its investigational fixed-dose, single-tablet "Quad" regimen of elvitegravir, cobicistat (formerly GS 9350), emtricitabine and tenofovir disoproxil fumarate. The Phase III clinical program for the Quad includes two studies (Studies 102 and 103) that will evaluate the Quad regimen versus a standard of care among HIV-1 infected antiretroviral treatment-naive adults.

"We are pleased to announce that the Quad Phase III clinical program is underway," said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. "Efficacy and safety results from the Phase II study suggest that the Quad may represent an important new option for patients with HIV. We look forward to further defining the clinical profile of the Quad in a larger number of patients in the Phase III trials."

Gilead is also examining cobicistat as a stand-alone boosting agent for other antiretrovirals, in particular protease inhibitors. Later this quarter, Gilead plans to initiate a Phase III clinical trial evaluating the efficacy, safety and tolerability of cobicistat-boosted atazanavir compared to ritonavir-boosted atazanavir, each in combination with Truvada (emtricitabine and tenofovir disoproxil fumarate).

Study Design

Study 102 is a randomized, double-blind clinical trial that will compare the efficacy, safety and tolerability of the Quad versus Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) over a 96-week period at 130 study sites in the United States and Puerto Rico. Eligible participants will be HIV-infected treatment-naive adults with HIV RNA levels greater than or equal to 5,000 copies/mL. Approximately 700 trial participants will be 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=350) or Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) (n=350).

Study 103 is a randomized, double-blind clinical trial that will compare the efficacy, safety and tolerability of the Quad versus ritonavir-boosted atazanavir and Truvada over a 96-week period at more than 200 study sites in North America, South America, Europe and Asia Pacific. Eligible participants will be HIV-infected treatment-naive adults with HIV RNA levels greater than or equal to 5,000 copies/mL. Approximately 700 trial participants will be 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=350) or ritonavir 100 mg and atazanavir 300 mg and emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (n=350).

The primary endpoint of both trials will be 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.

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.

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.
The fixed-dose single-tablet "Quad" regimen, elvitegravir and cobicistat are investigational products and have not yet been determined safe or efficacious in humans.

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 Australia.

The complete press release, which includes Truvada and Atripla safety information, is available online at http://www.gilead.com/pr_1411934.

For complete prescribing information for Truvada, visit www.Truvada.com.

For complete prescribing information for Atripla, visit www.Atripla.com.

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

4/16/10

Source

Gilead Sciences. Gilead Initiates Phase III Clinical Program Evaluating Single-Tablet, Once-Daily "Quad" Regimen for HIV. Press release. April 12, 2010.