Back HIV Treatment Experimental HIV Drugs FDA Advisors Favor Approval of 4-in-1 Elvitegravir Quad Pill for HIV

FDA Advisors Favor Approval of 4-in-1 Elvitegravir Quad Pill for HIV

alt

On May 11, 2012, the Antiviral Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) recommended approval of Gilead Sciences' 4-in-1 once-daily single-tablet antiretroviral regimen known as the Quad. A final decision in expected by late summer.

The committee voted 13 to 1 in favor of approving the Quad pill, which contains the next-generation integrase inhibitor elvitegravir, the novel pharmacoenhancer or "booster" cobicistat, and tenofovir/emtricitabine (the NRTI duo in Truvada, which the committee the day before recommended for HIV pre-exposure prophylaxis).

If the Quad is approved, it will be the third single-tablet regimen for HIV, joining Atripla (efavirenz/tenofovir/emtricitabine) and Complera (rilpivirine/tenofovir/emtricitabine), both also made by Gilead. The Quad is unusual in that the combination pill is being considered for approval before all of its components are approved as single agents.

As reported at this year's Conference on Retroviruses and Opportunistic Infections (CROI 2012) in March, the Quad was as effective as the widely used Atripla pill in suppressing HIV viral load, but with fewer neuropsychiatric side effects. A companion study found that the Quad also matched boosted atazanavir (Reyataz) in antiviral efficacy.

In Phase 3 Study 236-0102 -- a head-to-head comparison of non-nucleoside reverse transcriptase inhibitor single-tablet regimens in 700 treatment-naive patients -- 88% of participants in the Quad arm and 84% of those on Atripla achieved undetectable HIV viral load at 48 weeks. Similar proportions of patients discontinued therapy prematurely, but fewer in the Quad group stopped early due to adverse events. Quad recipients were more likely to report nausea, but less likely to experience several other symptoms including abnormal dreams, insomnia, dizziness, and skin rash.

Study 236-0103 compared the Quad to a popular protease inhibitor regimen, ritonavir-boosted atazanavir plus tenofovir/emtricitabine, in 708 previously untreated patients. Here, 90% of people in the Quad arm and 87% in the boosted atazanavir arm achieved undetectable HIV RNA at 48 weeks. Again, both regimens were generally well-tolerated, with similar proportions discontinuing due to adverse events.

In both studies, people taking the Quad had larger early increases in serum creatinine -- a marker of possible kidney impairment -- although this soon stabilized and did not progress over time. Researchers explained that cobicistat inhibits kidney tubular secretion, thereby altering estimated but not actual GFR (a measure of kidney function). Kidney toxicity is a concern with the Quad because tenofovir has also been linked to kidney problems is a small proportion of patients. The advisory panel recommended that people taking the Quad should have their kidney function monitored regularly.

The FDA is not required to follow its committees' recommendations but it usually does so. The full FDA is expected by August 27, according to Gilead.

5/11/12

Sources

S Pettypiece and R Flinn. Gilead’s HIV Quad Pill Wins Backing From FDA Advisers. Bloomberg News. May 11, 2012.

Gilead Sciences. FDA Advisory Committee Supports Approval of Gilead’s Once-Daily Quad Single Tablet Regimen for HIV. Press release. May 11, 2012.