CROI 2012: 4-in-1 Elvitegravir Quad Pill Matches Efavirenz and Atazanavir Combos

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The Quad single-tablet regimen, an all-in-one pill containing the experimental integrase inhibitor elvitegravir plus 2 other antiretroviral drugs and a novel boosting agent, was as effective as the widely used Atripla combination but with fewer neuropsychiatric side-effects, researchers reported at the 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012) this week in Seattle. In a companion study the Quad also matched boosted atazanavir (Reyataz).

Quad vs Atripla

Paul Sax from Brigham and Women's Hospital in Boston reported 48-week primary data from a Phase 3 trial (Study 236-0102) comparing 2 convenient single-tablet regimens.

The study enrolled 700 participants. Most (about 90%) were men, about two-thirds were white and the average age was 38 years. All were starting their first antiretroviral regimen. One-third had high baseline HIV viral load (> 100,000 copies/mL). The mean CD4 T-cell count was about 385 cells/mm3, but about 30% had levels below 350 cells/mm3 and 13% had less than 200 cells/mm3.

Participants were randomly assigned to take 1 of 2 all-in-one regimens: Gilead's Quad pill, containing the second-generation integrase inhibitor elvitegravir, the pharmacoenhancer cobicistat, tenofovir and emtricitabine, or else Atripla, containing the NNRTI efavirenz (Sustiva) plus tenofovir and emtricitabine.

Results

In this first fully-powered study comparing once-daily single-tablet HIV regimens, "Quad demonstrated non-inferior efficacy", the researchers concluded. The Quad was well-tolerated with "similar low rates of treatment discontinuation".

Prior studies have shown that cobicistat affects kidney tubule secretion of creatinine, but it does not appear to cause the type of damage seen with kidney-toxic drugs.

Coinvestigator Cal Cohen explained in an interview that it will be important for people taking the Quad to have their laboratory values monitored regularly to detect signs of kidney problems, which occur in about 1% of patients. "This is not the kind of drug where you can come in once a year," he said. "We need to find the few people with problems and get them on another drug."

Quad vs Atazanavir

Findings from a second parallel trial (Study 236-0103) were presented in a poster by Edwin DeJesus and colleagues. This study compared the Quad to a popular protease inhibitor regimen, ritonavir-boosted atazanavir plus tenofovir and emtricitabine.

This analysis included 708 treatment-naive participants with baseline characteristics similar to those of the population in the Atripla study.

Results

"Quad demonstrated non-inferior efficacy and was well tolerated at 48 weeks in this Phase 3 blinded active-controlled study in treatment-naive HIV-infected subjects," the researchers concluded. "These data support the use of Quad as a potential new [single-tablet regimen] option for initial HIV treatment."

Based on these findings, Gilead has submitted the Quad for regulatory approval in Europe, the US, Australia and Canada, with a decision from the US Food and Drug Administration expected by August 2012.

At an earlier presentation at the conference, researchers reported that the company is also working on a new Quad formulation that replaces tenofovir with its pro-drug GS-7340, which concentrates in cells and may cause fewer side-effects. 

Investigator affiliations:

Study 0102: Brigham and Women's Hosp, Harvard Med School, Boston, MA; Orlando Immunology Ctr, Orlando, FL; Anthony Mills MD, Inc, Los Angeles, CA; Stanford University, Palo Alto, CA; Community Res Initiative of New England, Boston, MA; Univ of North Carolina, Chapel Hill, NA; Johns Hopkins Univ School of Medicine, Baltimore, MD; Gilead Sciences, Foster City, CA.

Study 0103: Orlando Immunology Ctr, Orlando, FL; Univ of Bonn, Germany; Hennepin County Med Ctr, Minneapolis, MN; Saint Louis Hosp, Paris, France; Therapeutic Concepts PA, Houston, TX; Gilead Sciences, Foster City, CA, US

 3/13/12

References

P Sax, E DeJesus, A Mills, et al. Elvitegravir/Cobicistat/Emtricitabine/Tenofovir (Quad) Has Non-inferior Efficacy and Favorable Safety Compared to Efavirenz/Emtricitabine/Tenofovir in Treatment-naive HIV-1+ Subjects. 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012). Seattle, WA. March 5-8, 2012. Abstract 101.

E DeJesus, J Rockstroh, K Henry, et al. Week 48 Results of an Ongoing Global Phase 3 Study Comparing Elvitegravir/Cobicistat/Emtricitabine/Tenofovir (Quad) with Atazanavir/ritonavir plus Emtricitabine/Tenofovir in Treatment-naive HIV-1+ Subjects Showing Efficacy, Safety, and Pharmacokinetics. 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012). Seattle, WA. March 5-8, 2012. Abstract 627.

Other Sources

Gilead Sciences. Gilead’s Quad Single Tablet Regimen for HIV Non-Inferior to Atripla in Pivotal Phase 3 Study. Press release. March 7, 2012.

Gilead Sciences. Data Show Gilead’s Quad Regimen for HIV Non-Inferior to Protease-Based Regimen at 48 Weeks in Second Pivotal Phase 3 Study. Press release. March 7, 2012.