Biotech Values

[DewDiligence]

GILD Starts Phase-3 Trials of ‘Quad’ Pill for HIV

[As the name implies, Quad contains four drugs: the two constituents of Truvada; the integrase inhibitor, Elvitegravir; and the PK-booster, Cobicistat (f/k/a GS9350).

The phase-3 program consists of two 700-patient trials in the first-line setting: one trial comparing Quad to Atripla and one trial comparing Quad to Truvada+Reyataz. This makes sense insofar as Atripla and Truvada+Reyataz are the two most commonly used HIV regimens in the first-line setting.]

http://finance.yahoo.com/news/Gilead-Initiates-Phase-III-bw-1089604695.html?x=0&.v=1

›Monday April 12, 2010, 4:15 pm EDT

FOSTER CITY, Calif.--(BUSINESS WIRE)--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-naïve 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 [as previously reported]. Later this quarter, Gilead plans to initiate a Phase III clinical trial evaluating the efficacy, safety and tolerability of cobicistat-boosted atazanavir [Reyataz, the leading PI for HIV] 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-naïve 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-naïve 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. [This is a standard efficacy endpoint in HIV trials.] 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.‹