Phase
III Clinical Trial of Gilead's Investigational
Elvitegravir Meets 48-Week Primary Objective
Foster
City, Calif. -- March 23, 2011 -- Gilead Sciences, Inc.
(Nasdaq:GILD) today announced that the Phase III clinical
trial of its investigational antiretroviral agent elvitegravir,
a novel oral integrase inhibitor being evaluated for the
treatment of HIV-1 infection in treatment-experienced patients,
met its primary objective.
The primary endpoint of this study was non-inferiority at
week 48 of elvitegravir, dosed once daily, compared to raltegravir,
dosed twice daily, each administered with a background regimen
that includes a ritonavir-boosted protease inhibitor (PI)
and a second antiretroviral agent. Responses at 48 weeks
of elvitegravir met the statistical criteria of non-inferiority
as compared to raltegravir based on the proportion of subjects
who achieved and maintained HIV RNA levels (viral load)
of less than 50 copies/mL. Discontinuation rates due to
adverse events were comparable in both arms of the study.
Gilead plans to submit these data for presentation at a
scientific conference later this year.
On January 10, 2011, Gilead announced an amendment to the
design of this clinical trial, extending the blinded, randomized
period of the study to up to 96 weeks to obtain longer term
safety and efficacy data than originally planned. Based
on the achievement of the non-inferiority endpoint, patients
will continue to receive the regimen to which they were
randomized in a blinded fashion.
Elvitegravir is also being studied as part of Gilead's investigational
fixed-dose, single-tablet "Quad" regimen. The
Quad contains four Gilead compounds in a fixed-dose, single-tablet:
elvitegravir; cobicistat, a pharmacoenhancing or "boosting"
agent that increases blood levels of certain HIV medicines;
and Truvada (emtricitabine/tenofovir disoproxil fumarate).
The Quad is currently in Phase III testing. In addition,
cobicistat is being evaluated as a stand-alone boosting
agent for other antiretrovirals, in particular, protease
inhibitors.
"We are very pleased to have achieved the primary endpoint
in this clinical trial, as data from this study will support
regulatory filings for elvitegravir as well as Gilead's
investigational Quad pill," said Norbert Bischofberger,
PhD, Executive Vice President, Research and Development
and Chief Scientific Officer, Gilead Sciences. "By
analyzing these data now we will be in a better position
to advance filings as quickly as possible once data from
subsequent Phase III clinical trials in our Quad development
program become available later this year."
About the Elvitegravir Phase III Study
Study 145 is a randomized, double-blind, 48-week clinical
trial evaluating the non-inferiority of elvitegravir (n=351)
versus raltegravir (n=351), each administered with a background
regimen in HIV-infected treatment-experienced adults with
HIV RNA (viral load) of greater than or equal to 1,000 copies/mL.
Patients have documented viral resistance, as defined by
International AIDS Society-USA guidelines, or at least six
months of treatment experience with two or more different
classes of antiretroviral agents prior to screening.
Trial participants receive either once-daily elvitegravir
150 mg or twice-daily raltegravir 400 mg. Patients' background
regimens are based on the results of resistance testing
and include a fully-active ritonavir-boosted PI, and a second
agent that may be a nucleoside reverse transcriptase inhibitor
(NRTI), etravirine, maraviroc or enfuvirtide. Due to known
pharmacokinetic interactions, elvitegravir patients whose
background PI is either atazanavir or lopinavir receive
an 85 mg dose of elvitegravir.
The primary endpoint analysis indicated that 59.0 percent
of patients in the elvitegravir arm compared to 57.8 percent
in the raltegravir arm (95% CI for the difference: -6.0%
to +8.2%) achieved and maintained a viral load of less than
50 copies/mL through week 48. The predefined criterion for
non-inferiority was a lower bound of a two sided 95% CI
of -10 percent. The nature and frequency of Grade 3/4 adverse
events and laboratory abnormalities were similar between
the two arms.
The study is ongoing in a blinded fashion. Secondary endpoints
include various additional measures of the efficacy, safety
and tolerability of the two treatment regimens.
Additional information about the study can be found at www.clinicaltrials.gov.
The Quad, elvitegravir and cobicistat are investigational
products and have not yet been determined safe or efficacious
in humans.
About Elvitegravir
Elvitegravir is an HIV 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 Japan Tobacco Inc. (JT) in March
2005. Under the terms of Gilead's agreement with JT, Gilead
has exclusive rights to develop and commercialize elvitegravir
in all countries of the world, excluding Japan, where JT
retains rights.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers,
develops and commercializes innovative therapeutics in areas
of unmet medical need. The company's mission is to advance
the care of patients suffering from life-threatening diseases
worldwide. Headquartered in Foster City, California, Gilead
has operations in North America, Europe and Asia Pacific.
For more information on Gilead Sciences, please visit the
company's website at www.gilead.com
or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
On
March 23, Gilead Sciences announced that its investigational
integrase inhibitor taken, once-daily in combination with
a ritonavir-boosted protease inhibitor plus a third drug,
suppressed HIV replication as well as twice-daily 
