Experimental Quad Regimen For HIV-1 Naïve Patients Meets Primary Endpoint In Trial

Editor's Choice
Main Category: HIV / AIDS
Article Date: 15 Aug 2011 - 13:00 PDT


A Phase III clinical trial of "Quad" regimen including elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate for treatment naïve HIV-1 patients met its primary endpoint - non-inferiority compared to Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) at 48 weeks, Gilead Sciences Inc. announced. The Quad regimen is administered as a once-a-day, fixed-dose single-tablet.

88% of those in the Quad group achieved HIV viral load (RNA) of less than 50 copies/mL compared to 84% in the Atripla group at week 48.

Gilead added that among those in the Quad group, the mean 48-week rise in CD4 cell count from baseline was 239 cells/mm³ compared to 206 in the Atripla group. Both groups had similar Grade 3-4 adverse events and laboratory abnormalities, as were discontinuation rates due to adverse events.

Gilead says the company plans to submit its data at a scientific conference in 2012.

The Quad regimen consists of one tablet, that is taken orally once a day, and includes four of its own compounds:

• Elvitegravir, an integrase inhibitor (investigational)
• Cobicistat - another investigational compound that bolsters blood levels of specific HIV medications
• Truvada - emtricitabine/tenofovir disoproxil fumarate

The trials for the Quad regime include two Phase III studies - Study 102 and Study 103. They are comparing the Quad regime against standard treatments for HIV-1 treatment naïve patients.

Study 103 is a double-blind, randomized human study that compares the tolerability and safety of Quad against ritonavir-boosted atazanavir and Truvada. The results are expected during late summer or early fall this year.

Norbert Bischofberger, PhD, Executive VP, R&D and Chief Scientific Officer, Gilead Sciences, said:

"Achieving non-inferiority to the current standard of care in HIV therapy is a major developmental milestone for our Quad regimen. We are very pleased with these results, which are in line with our expectations and allow us to begin preparations for a U.S. regulatory filing in the first quarter of 2012."

Cobicistat is also being tested as a boosting agent for other antiretroviral medications, especially atazanavir, a protease inhibitor. This Phase III trial should have results during the last quarter of this year.

Study 102 is a randomized, double-blind study that compares the tolerability, safety and efficacy of the Quad regimen with Atripla over 96 weeks. The clinical trial is being performed at 130 sites in the USA and Puerto Rico. Study participants had never been treated for HIV before (treatment naïve), their HIV RNA levels are at least 5,000 copies/mL. They were randomly selected to be administered either a once-daily tablet containing elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (n=348) or Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) (n=352).

The study's primary endpoint is the percentage of participants who achieve HIV RNA levels of less than 50 copies/mL at 48 weeks. Its secondary objective will assess its tolerability, safety and efficacy at 96 weeks of treatment.

Gilead wrote on its website:

"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."

Gilead adds that elvitegravir and cobicistat are still investigational compounds - they have not yet been cleared for safety or efficacy.

Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

• Additional
• References
• Citations