Days after winning FDA approval of Complera a.k.a. Btripla, the follow-on to HIV blockbuster Atripla Gilead Sciences Inc. unveiled the first Phase III data with the drug that's expected to blow them both out of the water: Quad.
As anticipated, Quad met its primary endpoint of non-inferiority to Atripla in viral load reduction, with 88 percent of Quad patients achieving HIV RNA levels below 50 copies/mL through week 48, compared to 84 percent of Atripla patients.
But while Quad was indeed non-inferior to and even numerically better than Atripla, it fell short of showing statistically significant superiority. ISI Group analyst Mark Schoenebaum wrote in a research note that while a 5 percent to 6 percent delta "may have resulted in superiority," Quad came in at 4 percent.
That little difference might turn out to be a big deal, if a physician survey from Jefferies & Co. is any indication. The survey of 99 HIV physicians queried before the Quad data were released showed that Quad would be likely to gain substantial share from Atripla if the Phase III data demonstrated superiority, but that the doctors would continue to prefer Atripla if Quad showed only noninferiority. The physicians also showed a strong preference for generic Atripla, when it becomes available in 2018.
That could be bad news for Gilead. Atripla (emtricitabine/efavirenz/tenofovir disoproxil fumarate) generated $2.93 billion last year, and while analysts expect Complera (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) to offer some benefits, such as an improved safety profile, the real long-term growth driver for Gilead's continued HIV success is Quad (cobicstat/elvitegravir/emtricitabine/tenofovir disoproxil fumarate), which analysts have projected could become a $4 billion product. (See BioWorld Today, Aug. 12, 2011.)
Some analysts remain optimistic about Quad's prospects. "Based on our prior discussions with physicians and payers, we do not believe Quad needed to demonstrate superiority over Atripla to be commercially successful," wrote Brian Abrahams of Wells Fargo Securities in a research note.
Much depends on the details of how Quad and Atripla compared in the Phase III trial, and Gilead is saving those details for presentation at a scientific conference.
What the Foster City, Calif.-based biotech did reveal, in addition to the primary endpoint data, was a statistically significant mean 48-week increase in CD4 cell count of 239 cells/mm3 for Quad patients versus 206 cells/mm3 for Atripla patients (p=0.009). That finding, combined with the trend toward superiority for viral load, bodes well for Quad on the efficacy front.
On the safety front, however, analysts were less certain. Gilead said only that the frequency of Grade 3-4 adverse events and the discontinuation rates due to adverse events were similar for both drugs. On the one hand, that means there was nothing new or unexpected safety-wise, but on the other hand, Quad had beaten Atripla in terms of adverse events and discontinuation rates in Phase II, and folks were mildly disappointed that the Phase III data didn't show the same, at least not given the limited information disclosed thus far.
"The key potential advantage for Quad is an improved tolerability profile vs. Atripla, and details on the relative safety profiles of the two regimens were limited," wrote Abrahams.
The Phase III trial, dubbed Study 102, was a 700-patient randomized, double-blind trial comparing Quad to Atripla over a 96-week period. Although the primary endpoint was measured at week 48, secondary endpoints will be measured through week 96 so the trial is continuing in a blinded fashion.
Gilead anticipates beginning preparations to file for approval of Quad in the first quarter of 2012. A second Phase III trial, dubbed Study 103, is comparing Quad to ritonavir-boosted Reyataz (atazanavir, Bristol-Myers Squibb Co.) and Gilead's Truvada (emtricitabine/tenofovir disoproxil fumarate), with data expected later this quarter.
Shares of Gilead (NASDAQ:GILD) dipped 16 cents to close at $37.27 on Monday.