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At 48 weeks of treatment in Study 103, Quad demonstrated comparable
efficacy to the atazanavir-based regimen, with 90 percent of Quad
patients compared to 87 percent of patients receiving ATV/r plus Truvada
achieving HIV RNA (viral load) less than 50 copies/mL, using the
“The 90 percent response rate demonstrated by the Quad in this study is
one of the highest we have seen in any large, randomized HIV clinical
trial of an antiretroviral regimen conducted to date,” said
The discontinuation rate due to adverse events was comparable among patients taking Quad (4 percent) and the atazanavir-based regimen (5 percent). Elevated bilirubin levels (grades 3-4) were observed in 1 percent of patients in the Quad arm, compared to 58 percent in the atazanavir-based arm. Quad patients also experienced significantly lower increases in triglyceride levels (+8 mg/dL) compared to those receiving the atazanavir-based regimen (+23 mg/dL).
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 from Study 103 on
Gilead submitted a U.S. New Drug Application for Quad on
Study 103
Study 103 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=353) versus atazanavir 300 mg boosted by
ritonavir 100 mg (ATV/r) plus Truvada (n=355) among HIV-infected
treatment-naïve adults with baseline HIV RNA levels greater than 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 4.88 log10 copies/mL and mean CD4 cell count of 364 cells/mm3. Patients in the atazanavir-based arm had a median HIV RNA of 4.86 log10 copies/mL and mean CD4 cell count of 375 cells/mm3. Across both arms, 41 percent of patients had HIV RNA greater than 100,000 copies/mL and 13 percent had CD4 counts less than or equal to 200 cells/mm3.
Patients in both arms experienced similar increases in CD4 cell counts
(mean increase of 207 cells/mm3 for Quad and 211 cells/ mm3
for ATV/r plus Truvada). The virologic failure rate was 5 percent for
both treatment regimens based on a component of the
The most common adverse events occurring in at least 10 percent of patients in either arm of the study were diarrhea, nausea, upper respiratory infection, headache, fatigue and ocular icterus. The most common adverse events were similar across both treatment arms with the exception of ocular icterus (associated with elevated bilirubin levels), which was less frequent for the Quad arm than for the ATV/r plus Truvada arm of the study (1 and 14 percent, respectively).
With the exception of elevated bilirubin levels among patients receiving atazanavir-based therapy, grade 3-4 laboratory abnormalities were similar for both treatment regimens, with only elevated creatine kinase occurring in more than 5 percent of patients (6 percent for the Quad and 7 percent for ATV/r plus Truvada). Lipid increases were comparable between study arms, with the exception of the higher triglyceride elevations observed among patients taking the atazanavir-based regimen (p=0.006).
Both treatment regimens had comparable renal profiles, with median increases in serum creatinine of 0.12 mg/dL for the Quad and 0.08 mg/dL for ATV/r plus Truvada. Bone safety profiles were also similar, with a median change from baseline in hip bone density of -2.87 percent for the Quad and -3.59 percent for ATV/r plus Truvada (p=0.12).
The study 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.
The Quad, elvitegravir and cobicistat are investigational products and their safety and efficacy have not yet been established.
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
from
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.
About
Forward-Looking Statement
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 Truvada is available at www.Truvada.com.U.S. full prescribing information for Atripla is available at www.Atripla.com.
Truvada is a registered trademark of
For more information on
Source:
Gilead Sciences, Inc.Susan Hubbard, 650-522-5715 (Investors)Erin Rau, 650-522-5635 (Media)
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