Gilead Sciences, Inc. (Nasdaq:GILD) today announced 24-week data
from a Phase II clinical trial evaluating three doses of GS 9137
(elvitegravir), a novel oral HIV integrase inhibitor. The data,
presented this week at the 14th Conference on Retroviruses and
Opportunistic Infections (CROI) by Andrew Zolopa, MD, Associate
Professor, Stanford School of Medicine (Abstract #J-1007, Late Breaker
#143LB), show statistically superior reductions in viral load among
HIV-positive treatment-experienced patients receiving 125 mg of
once-daily GS 9137 boosted with 100 mg of ritonavir, compared to those
receiving a boosted protease inhibitor, both in combination with an
optimized background regimen.
"Integrase inhibitors represent a promising new class in the field
of HIV treatment, and I am encouraged by these Phase II data for
once-daily GS 9137," said Dr. Zolopa. "As a clinician, I am frequently
reminded of the importance of expanding simplified treatment options
for people living with HIV, particularly among treatment-experienced
patients who have developed resistance to many existing medications."
Integrase inhibitors are an investigational class of
antiretrovirals that interfere with HIV replication by blocking the
ability of the virus to integrate into the genetic material of human
cells. Novel classes of HIV-fighting drugs are needed as patients live
longer and exhaust currently available treatment options.
About the Study
This ongoing Phase II study is a partially-blinded, randomized,
active-controlled, 48-week clinical trial to evaluate the
non-inferiority of once-daily GS 9137 versus boosted comparator
protease inhibitors (CPI/r) in HIV-infected treatment-experienced
patients. Two hundred and seventy-eight (278) patients were randomized
and received either once-daily GS 9137 20 mg (n=71), 50 mg (n=71) or
125 mg (n=73), each with 100 mg of ritonavir, or CPI/r (n=63), all in
combination with an optimized background regimen of two or more
nucleoside reverse transcriptase inhibitors (NRTIs) with or without
the fusion inhibitor T-20. Patients receiving T-20 as part of their
background regimen were stratified across treatment arms. At study
entry, patients were required to have HIV RNA (viral load) of at least
1,000 copies/mL and at least one protease resistance mutation. There
was no CD4 cell count entry criterion for study participants.
At baseline, study participants had a mean viral load of 4.59
log10 copies/mL, a mean CD4 cell count of 185 cells/mm3 and HIV
isolated from patients exhibited a median of 11 protease resistance
mutations. The independent data safety monitoring board reviewed week
eight data and based on its recommendation, the GS 9137 20 mg arm was
closed due to a high rate of virologic failure. Patients in this arm
of the study were offered open-label GS 9137 125 mg. The addition of
darunavir or tipranavir to the GS 9137 study arms was also permitted
at week eight following the availability of data demonstrating a lack
of drug interactions between both protease inhibitors and GS 9137.
These interaction data were unavailable at the initiation of the
study, precluding the use of protease inhibitors in the optimized
background regimen in the GS 9137 arms at study entry. Prior to week
24, 15 percent of patients in the GS 9137 50 and 125 mg arms of the
study added either darunavir or tipranavir and 37 percent of patients
in the CPI/r arm who met protocol-defined criteria for virologic
failure were switched to open-label GS 9137.
Rapid and potent antiviral activity was observed in the 50 and 125
mg GS 9137 arms of the study. The primary endpoint of the study was
DAVG24, a measure of viral load reduction over 24 weeks. The mean
DAVG24 for patients receiving 50 mg of once-daily boosted GS 9137 was
-1.4 log10 copies/mL versus -1.2 log10 copies/mL for the comparator
arm (95% confidence interval, -0.6, 0.2; p=0.27). The mean DAVG24 for
patients receiving 125 mg of once-daily boosted GS 9137 was -1.7 log10
copies/mL versus -1.2 log10 copies/mL for the comparator arm (95%
confidence interval, -0.8, -0.05; p=0.02).
Among patients who received GS 9137 125 mg, the durability of
antiviral response was related to having active agents in the
optimized background regimen. In the GS 9137 125 mg arm, patients
receiving T-20 for the first time, or those who had at least one
active NRTI in their background regimen (n=47), experienced
significantly greater mean reductions in viral load at 24 weeks
compared to those with no active NRTIs and no first use of T-20 (n=26;
-2.1 log10 copies/mL versus -0.7 log10 copies/mL, respectively; p less
than 0.001). Active agents were determined using Genotypic
Susceptibility Scores (GSS), a measure of viral susceptibility to an
antiretroviral agent.
At 16 weeks, 38 percent (27/71) of patients in GS 9137 50 mg arm
and 40 percent (29/73) of patients in the GS 9137 125 mg arm achieved
HIV RNA less than 50 copies/mL compared to 30 percent (19/63) of
patients in the CPI/r arm of the study, using an intent to treat
analysis where missing equals failure. At 24 weeks, 32 percent (23/71)
of patients in the GS 9137 50 mg arm and 36 percent (26/73) of
patients in the GS 9137 125 mg arm achieved HIV RNA less than 50
copies/mL compared to 27 percent (17/63) of patients in the CPI/r arm.
At 16 weeks, mean increases in CD4 cell count among patients receiving
50 mg and 125 mg of GS 9137 were 52 and 61 cells/mm3 versus 28
cells/mm3 for the comparator arm. At 24 weeks, the increase in CD4
cells was also similar across the arms (53 and 57 versus 53 cells/mm3,
respectively). These differences were not statistically significant.
GS 9137 was well tolerated. No dose relationship was observed in
treatment-emergent Grade 3 or 4 adverse events, laboratory
abnormalities or discontinuations of study drug, and incidences of
events across these safety and tolerability parameters were similar
between the GS 9137 and CPI/r arms of the study.
"We are very encouraged by the rapid and potent antiviral activity
observed with the 125 mg dose of GS 9137, particularly in this
heavily treatment-experienced population," said Norbert Bischofberger,
PhD, Executive Vice President, Research and Development, Gilead
Sciences. "We are currently in the process of reviewing the full data
set from this study with the FDA, along with plans for registrational
studies."
About GS 9137
GS 9137, also known as JTK-303, was licensed by Gilead from Japan
Tobacco Inc. (JT) in March 2005. Under the terms of the company's
agreement with JT, Gilead has exclusive rights to develop and
commercialize GS 9137 in all countries of the world, excluding Japan
where JT retains rights. As an investigational compound, GS 9137 has
not yet been determined safe or efficacious in humans for its ultimate
intended use.
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 Australia.
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 risks
related to Gilead's ability to successfully develop and commercialize
GS 9137. For example, the safety and efficacy data from additional
clinical studies may not warrant further development of this compound,
and initiating and completing clinical trials may take longer or cost
more than expected. Future discussions with the FDA may impact the
amount of data needed and timelines for review, and Gilead's clinical
trial protocol design, clinical endpoint and statistical analyses for
any additional trials will be subject to FDA review and approval. In
addition, integrase inhibitors represent a relatively new class of
compounds that has not had a long history of clinical research and
development. Therefore, Gilead may face challenges in clinical trial
protocol design and trial enrollment, and the results of clinical
trials involving integrase inhibitors may be less predictable than
with other drug candidates for the treatment of HIV. 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 the
Gilead's Annual Report on Form 10-K for the year ended December 31,
2005 and Reports on Form 10-Q for the first three quarters of 2006,
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.
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.
