March 07, 2012
Gilead’s Quad Single Tablet Regimen for HIV Non-Inferior to Atripla® in Pivotal Phase 3 Study
-- Quad Currently Under Review for Marketing Approval by U.S. and European Regulatory Agencies --
“These data show that the Quad is as effective as a current standard of
care in HIV therapy. The safety profile of Quad was also comparable to
that of Atripla, and was better tolerated in terms of key neurological
side effects,” said
The study found that at 48 weeks of treatment, 88 percent of Quad
patients compared to 84 percent of Atripla patients achieved HIV RNA
(viral load) less than 50 copies/mL, based on the
The Phase 3 clinical program for Quad includes two studies (Studies 102
and 103) that each evaluate the Quad regimen versus a standard of care
among HIV-1 infected antiretroviral treatment-naïve adults. Gilead
announced topline results for Studies 102 and 103 on
Study 102 is a randomized (1:1), double-blind Phase 3 clinical trial
comparing the efficacy, safety and tolerability of the Quad
(elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir
disoproxil fumarate 300 mg) (n=348) versus Atripla (efavirenz 600
mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) (n=352)
among HIV-infected treatment-naïve adults with HIV RNA levels greater
than or equal to 5,000 copies/mL. The primary endpoint of the study is
the proportion of patients achieving HIV RNA levels less than 50
copies/mL at 48 weeks of treatment, per the
At baseline, patients in the Quad arm had a median HIV RNA of 4.75 log10 copies/mL and mean CD4 cell count of 391 cells/mm3. Patients in the Atripla arm had a median HIV RNA of 4.78 log10 copies/mL and mean CD4 cell count of 382 cells/mm3. Across both arms, 33 percent of patients had HIV RNA greater than 100,000 copies/mL, and 13 percent of patients had CD4 counts less than or equal to 200 cells/mm3.
Among patients with baseline HIV RNA greater than 100,000 copies/mL, 84
percent and 82 percent of Quad and Atripla patients, respectively,
achieved viral load less than 50 copies/mL based on the
Four percent of Quad patients and 5 percent of Atripla patients discontinued treatment due to adverse events. The most common adverse events occurring in greater than 10 percent of patients in either treatment arm included diarrhea, nausea, abnormal dreams, upper respiratory infections, headache, fatigue, insomnia, depression, dizziness and rash. Among adverse events occurring in at least 10 percent of patients, neuropsychiatric side effects were less common among Quad patients, including abnormal dreams (15 percent for Quad vs. 27 percent for Atripla), dizziness (7 vs. 24 percent) and insomnia (9 vs. 14 percent). Rash was also less likely to occur among Quad patients (6 percent for the Quad vs. 12 percent for Atripla). Nausea (mostly grade 1) was more frequent among Quad patients compared to Atripla (21 percent vs. 14 percent, respectively).
There was a similar incidence of laboratory abnormalities (grades 3-4) across both arms of the study. Laboratory abnormalities (grades 3-4) occurring in greater than five patients in either treatment arm included creatine kinase, AST, ALT, GGT, neutrophils, amylase and hematuria. Increases in total cholesterol and LDL were lower for the Quad (+10 mg/dL total cholesterol and +10 mg/dL LDL) compared to Atripla (+19 mg/dL total cholesterol and +17 mg/dL LDL) at week 48 (total cholesterol, p<0.001; LDL, p=0.001). The median increases in serum creatinine were 0.14 mg/dL for Quad and 0.01 mg/dL for Atripla.
Study 102 is ongoing in a blinded fashion. After week 192, 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. Additional information about the study can be found at www.clinicaltrials.gov.
About the Quad
The Quad contains four Gilead compounds in a complete once-daily, single tablet regimen: elvitegravir; cobicistat, a “boosting” agent that enables elvitegravir once-daily dosing; and Truvada®, which is a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate.
Elvitegravir is an integrase inhibitor. Unlike other classes of
antiretroviral agents, integrase inhibitors interfere with HIV
replication by blocking the ability of the virus to integrate into the
genetic material of human cells. Elvitegravir was licensed by Gilead
Cobicistat is Gilead’s proprietary potent mechanism-based inhibitor of cytochrome P450 3A (CYP3A), an enzyme that metabolizes drugs in the body. In addition to studying the agent as part of the Quad, Gilead is also examining cobicistat’s potential in boosting commercially available HIV protease inhibitors.
The Quad, elvitegravir and cobicistat are investigational products and their safety and efficacy have not yet been established.
This press release includes forward-looking statements, within the
meaning of the Private Securities Litigation Reform Act of 1995, that
are subject to risks, uncertainties and other factors, including the
risk that the
U.S. full prescribing information for Atripla is available at www.Atripla.com.
U.S. full prescribing information for Truvada is available at www.Truvada.com.
Truvada is a registered trademark of
Atripla is a registered trademark of
For more information on
Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Erin Rau, 650-522-5635 (Media)