On A Roll: Gilead's Top-Line Quad Data Stack Up To Atripla

After announcing FDA approval of a new HIV combination last week, Gilead released positive comparative data on the Quad pill Aug. 15.

In the midst of launching its new triple combination antiretroviral Complera, following FDA approval just a week ago, Gilead Sciences Inc. continued the positive-news streak with the release of solid top-line data on its "Quad" combination for HIV Aug. 15.

The once-daily Quad tablet is considered critical to Gilead's efforts to maintain its dominance in the HIV treatment market into the next decade. But to be successful, the Quad will need to demonstrate benefits over the existing standard of care. Gilead is hoping to show the Quad - a fixed-dose combination of Gilead's blockbuster Truvada (emtricitabine and tenofovir) and two investigational drugs, the integrase inhibitor elvitegravir and the booster cobicistat - is at least as effective as the standard of care with better tolerability.

Investors got some assurance the drug is on track Aug. 15 with the release of positive top-line data from one of two Phase III trials showing the Quad was non-inferior to Atripla, the existing standard of care triple combination for the treatment of HIV, also marketed by Gilead.

But Gilead released few details on the safety and tolerability, which will be key to the drug's ultimate success. Gilead said it plans to present the full data at a scientific conference early next year and is on track to begin preparing a regulatory filing in the first quarter of 2012.

The first of two Phase III studies, Study 102, compared the Quad to Atripla, which combines Truvada with Bristol-Myers Squibb Co.' s non-nucleoside reverse transcriptase inhibitor Sustiva (efavirenz). A second Phase III trial, Study 103, comparing the Quad to ritonavir-boosted Reyataz (atazanavir) and Truvada, is ongoing with results expected later in the third quarter.

Study 102 met its primary endpoint, non-inferiority at week 48 compared to Atripla, with 88% of patients treated with the Quad compared to 84% of patients treated with Atripla achieving HIV RNA of less than 50 copies/mL. The mean 48-week increase in CD4 cell count from baseline was 239 cells/mm in the Quad arm compared to 206 cells/mm in the Atripla arm. The frequency of Grade 3-4 adverse events and laboratory abnormalities were similar between the two treatment groups, the firm said. The study is continuing in a blinded fashion through 96 weeks.

Earlier Phase II data showed the Quad had significantly fewer adverse events related to central nervous system disorders.

Analysts accepted the top-line data as a positive turn of events for Gilead, despite the limited safety details. "There were hopes for superiority of the Quad, but we think that this result still shows 1) a high likelihood of Quad approval and 2) market differentiation of the Quad, which ultimately is what matters," JP Morgan analyst Geoff Meacham said in a same-day research note.

RW Baird & Co. analyst Thomas Russo agreed. "We'd buy on any weakness following Quad Phase III success," he said in a note. "Top-line results and a quick company check-in suggest Quad fulfilled our expectations: efficacy non-inferior to Gilead's own 'gold standard' with no major controversy in those details, good safety and differentiating tolerability - its original reason for being."

Like other biotechs, Gilead's stock has been hit by the tumultuous market recently - but more specific to Gilead, the company also has experienced protracted overhang, with Wall Street anxious about the company's ability to successfully manage the life of its HIV franchise; patents protecting Viread (tenofovir) and Truvada are due to expire from 2017 to 2021.

The patent protection for Bristol's Sustiva, one of the components of Atripla, will expire in 2013, and the availability of a generic could pose an earlier threat to that franchise as well. Gilead is looking to switch patients to Complera before that patent expiration becomes a reality. The company is launching the new triple combination this week. Complera combines Truvada with a new NNRTI, Johnson & Johnson's Edurant (rilpivirine). Gilead announced FDA approval of Complera Aug. 10 (Also see "Gilead Complera Launch Imminent Following FDA Approval" - Pink Sheet, 11 Aug, 2011.).

Sales of Atripla, Truvada and Viread were about $6.31 billion in 2010, representing the bulk of Gilead's $7.95 billion in sales.

-Jessica Merrill ([email protected])