Gilead Sciences, Inc. (Nasdaq:GILD) today announced Phase III
clinical trial results from the pivotal Study 145 showing that its
investigational antiretroviral elvitegravir, a novel oral integrase
inhibitor being evaluated for the treatment of HIV-1 infection, was
non-inferior to the integrase inhibitor raltegravir after 48 weeks
of therapy in treatment-experienced patients. In the study,
elvitegravir (150 mg or 85 mg) dosed once daily was compared to
raltegravir (400 mg) dosed twice daily. Each integrase inhibitor
was administered with a background regimen that included a
ritonavir-boosted protease inhibitor (PI) and a second
antiretroviral (ARV). These data are being presented today in a
late-breaker session (LB# WELBB05) at the 6th International AIDS
Society Conference on HIV Pathogenesis, Treatment and Prevention
(IAS 2011) in Rome, Italy.
“Because many treatment-experienced HIV patients have developed
resistance to currently available antiretrovirals, identifying
novel therapeutic options from the integrase inhibitor class is
critical,” said Professor Jean-Michel Molina, MD, PhD, principal
investigator, Hôpital Saint Louis in Paris and University of Paris
7. “These data suggest that elvitegravir may be an effective option
for patients and may also have the potential for more convenient,
once-daily dosing as part of combination HIV therapy.”
At 48 weeks of treatment in Study 145, 59 percent of patients
receiving ritonavir-boosted elvitegravir achieved and maintained
HIV RNA levels (viral load) of less than 50 copies/mL, compared to
58 percent of patients receiving raltegravir, based on the Time to
Loss of Virologic Response algorithm (TLOVR). Discontinuation rates
due to adverse events, and safety and resistance profiles were
comparable in both arms of the study.
“These data are an important component of the regulatory filings
for elvitegravir as both a stand-alone product and as part of the
Quad single-tablet regimen in the United States and Europe in
2012,” said Norbert Bischofberger, PhD, Executive Vice President,
Research and Development and Chief Scientific Officer, Gilead
Sciences. “We believe elvitegravir, cobicistat and the Quad have
the potential to be important new components of HIV therapy.”
Gilead’s investigational fixed-dose, single-tablet Quad regimen,
which is currently in two Phase III studies, contains four Gilead
compounds in a single pill: elvitegravir; cobicistat, an
investigational pharmacoenhancing or “boosting” agent that
increases blood levels of certain HIV medicines; Viread® (tenofovir
disoproxil fumarate); and Emtriva® (emtricitabine). Phase III study
results are expected in the third quarter of this year.
About the Elvitegravir Phase III
Study
Study 145 is a double-blind, multicenter, randomized (1:1),
active-controlled 96-week clinical trial evaluating the
non-inferiority of ritonavir-boosted 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 enrolled in
the trial were required to have documented viral resistance and/or
at least six months of treatment experience with two or more
different classes of ARVs prior to screening.
Trial participants received either once-daily elvitegravir 150
mg or 85 mg or twice-daily raltegravir 400 mg. Patients’ background
regimens were based on the results of resistance testing and
included a fully-active ritonavir-boosted PI, and a second
investigator-selected agent that was permitted to be a nucleoside
or nucleotide reverse transcriptase inhibitor (NRTI), etravirine,
maraviroc or enfuvirtide. The most common background regimen was
Viread and ritonavir-boosted darunavir in 24 percent of patients.
Due to known pharmacokinetic interactions, patients randomized to
elvitegravir whose background PI was either atazanavir or lopinavir
received an 85 mg dose of elvitegravir.
At baseline, the mean HIV RNA for the intent-to-treat (ITT)
population (702 patients) was 4.26 log10 copies/mL and the mean CD4
cell count was 262 cells/mm3. Twenty-six percent of patients had
HIV RNA greater than 100,000 copies/mL, and 45 percent of patients
had CD4 cell counts less than or equal to 200 cells/mm3. The
percentage of patients with baseline resistance to two or more ARV
classes was 62 percent. The mean age of the study population was
45, and 82 percent were male.
After 48 weeks of treatment, 59 percent of elvitegravir patients
compared to 58 percent of raltegravir patients achieved and
maintained a viral load of less than 50 copies/mL using the TLOVR
algorithm (ITT population; non-inferiority p=0.001; 95% CI, -6.0%
to +8.2%). Patients receiving elvitegravir experienced a similar
mean increase in CD4 cell counts from baseline at week 48 compared
to those receiving raltegravir (138 vs. 147 cells/mm3,
respectively).
Nine patients (3 percent) receiving elvitegravir and 15 patients
(4 percent) receiving raltegravir discontinued treatment due to
adverse events. The Grade 2-4 adverse events occurring in greater
than or equal to 3 percent of patients in either treatment arm were
diarrhea, upper respiratory tract infection, bronchitis, back pain,
depression, sinusitis, arthralgia, nausea and urinary tract
infection. The incidence of these adverse events was similar in
both treatment arms, with the exception of diarrhea which occurred
in 12 percent of patients in the elvitegravir arm and 7 percent of
patients in the raltegravir arm. The Grade 3 or 4 serum laboratory
abnormalities occurring in greater than 5 patients in either
treatment arm were amylase, total bilirubin, cholesterol,
triglycerides, hyperglycemia, GGT, neutrophils, creatine kinase,
ALT and AST. The incidence of these laboratory abnormalities was
similar in the elvitegravir-treated and the raltegravir-treated
arms, with the exception of GGT (3 and 6 percent, respectively),
ALT (2 and 5 percent, respectively) and AST (1 and 5 percent,
respectively), which were higher in the raltegravir-treated
arm.
Drug resistance rates were also similar in both study arms. In
the elvitegravir arm, 16 of the 60 patients who experienced
virologic failure exhibited integrase resistance, while 15 of the
72 patients who experienced virologic failure in the raltegravir
arm exhibited integrase resistance.
On January 10, 2011, Gilead announced an amendment to the design
of Study 145, extending the blinded, randomized period of the study
from the originally planned 48 weeks to 96 weeks in order to obtain
longer-term safety and efficacy data. 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.
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.
Elvitegravir, cobicistat and the Quad 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 ARVs, 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.
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 Gilead will not complete the Phase III
clinical studies of elvitegravir and the Quad in the currently
anticipated timelines. In addition, Gilead may obtain unfavorable
results from these studies, may need to modify or delay its studies
or perform additional trials, and may fail to obtain approvals for
these antiretroviral products from the regulatory authorities, and
marketing approval, if granted, may have significant limitations on
its use. As a result, elvitegravir or the Quad may never be
successfully commercialized. Further, Gilead may make a strategic
decision to discontinue development of elvitegravir or the Quad if,
for example, it believes commercialization will be difficult
relative to other opportunities in its pipeline. These risks,
uncertainties and other factors could cause actual results to
differ materially from those referred to in the forward-looking
statements. The reader is cautioned not to rely on these
forward-looking statements. These and other risks are described in
detail in Gilead's Quarterly Report on Form 10-Q for the quarter
ended March 31, 2011, as filed with the U.S. Securities and
Exchange Commission. All forward-looking statements are based on
information currently available to Gilead, and Gilead assumes no
obligation to update any such forward-looking statements.
Emtriva and Viread are registered trademarks of
Gilead Sciences, Inc.
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.
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