- If Approved, SOF/VEL Would be the First All-Oral Pan-Genotypic
Single Tablet Regimen for Chronic HCV-
- U.S. NDA and European MAA Submissions Planned for Q4 2015 -
Gilead Sciences, Inc. (Nasdaq:GILD) today announced topline results from
four international Phase 3 clinical studies (ASTRAL-1, ASTRAL-2,
ASTRAL-3 and ASTRAL-4) evaluating a once-daily, fixed-dose combination
of the nucleotide analog polymerase inhibitor sofosbuvir (SOF) with
velpatasvir (VEL), an investigational pangenotypic NS5A inhibitor,
for the treatment of genotype 1-6 chronic hepatitis C virus (HCV)
infection.
In the ASTRAL-1, ASTRAL-2, and ASTRAL-3 studies, 1,035 patients with
genotype 1-6 HCV infection received 12 weeks of SOF/VEL. Among these
patients, 21 percent had compensated cirrhosis and 28 percent had failed
prior treatments. The ASTRAL-4 study randomized 267 patients with
decompensated cirrhosis (Child-Pugh class B) to receive 12 weeks of
SOF/VEL with or without ribavirin (RBV), or 24 weeks of SOF/VEL. The
primary endpoint for all studies was SVR12.
The intent-to-treat SVR12 rates observed in the ASTRAL studies are
summarized in the table below. Complete results from all four studies
will be presented at future scientific conferences.
Study
|
|
Population
|
|
N
|
|
Treatment
|
|
Duration
|
|
SVR12 Rates
|
ASTRAL-1
116 patients received placebo (SVR12=0%)
|
|
Genotypes 1,2,4,5,6
19 percent (121/624) with cirrhosis
|
|
624
|
|
SOF/VEL
|
|
12 weeks
|
|
Overall: 99% (618/624)
GT1: 98% (323/328)
GT2: 100% (104/104)
GT4: 100% (116/116)
GT5: 97% (34/35)
GT6: 100% (41/41)
|
ASTRAL-2
|
|
Genotype 2
14 percent (38/266) with cirrhosis
|
|
134
|
|
SOF/VEL
|
|
12 weeks
|
|
99% (133/134)
|
|
|
132
|
|
SOF+RBV
|
|
12 weeks
|
|
94% (124/132)
|
ASTRAL-3
|
|
Genotype 3
30 percent (163/552) with cirrhosis
|
|
277
|
|
SOF/VEL
|
|
12 weeks
|
|
95% (264/277)
|
|
|
275
|
|
SOF+RBV
|
|
24 weeks
|
|
80% (221/275)
|
ASTRAL-4
|
|
Genotypes 1-6
All with Child-Pugh class B (decompensated) cirrhosis
|
|
90
|
|
SOF/VEL
|
|
12 weeks
|
|
83% (75/90)
|
|
|
87
|
|
SOF/VEL+RBV
|
|
12 weeks
|
|
94% (82/87)
|
|
|
90
|
|
SOF/VEL
|
|
24 weeks
|
|
86% (77/90)
|
|
|
|
|
|
|
|
|
|
|
|
Of the 1,035 patients treated with SOF/VEL for 12 weeks in the ASTRAL-1,
ASTRAL-2 and ASTRAL-3 studies, 1,015 (98 percent) achieved the primary
efficacy endpoint of SVR12. Of the 20 patients who did not achieve
SVR12, 13 patients (1.3 percent) experienced virologic failure and seven
did not complete an SVR12 visit (e.g., lost to follow-up). Twelve of the
13 virologic failure patients relapsed (two genotype 1 HCV-infected
patients and 10 genotype 3 HCV-infected patients). There was one patient
with documented reinfection. No patients with genotype 2, 4, 5 or 6 HCV
infection had virologic failure.
Patients treated with SOF/VEL for 12 weeks in these three studies had
similar adverse events compared with placebo-treated patients in
ASTRAL-1. Two patients (0.2 percent) treated with SOF/VEL for 12 weeks,
one each in ASTRAL-1 and ASTRAL-2, discontinued treatment due to adverse
events. The most common adverse events were headache, fatigue and nausea.
In ASTRAL-4, patients with Child-Pugh class B cirrhosis receiving
SOF/VEL+RBV achieved higher SVR12 rates than patients receiving SOF/VEL
for 12 or 24 weeks. Among genotype 1 and 3 patients treated with
SOF/VEL+RBV for 12 weeks, the SVR12 rates were 96 percent and 85
percent, respectively.
The most common adverse events across all arms of ASTRAL-4 were fatigue,
nausea and headache. Anemia, a common side effect associated with RBV,
was reported in 31 percent of patients in the SOF/VEL+RBV arm and in 4
percent and 3 percent of patients treated with SOF/VEL for 12 or 24
weeks, respectively. Treatment emergent serious adverse events occurred
in 18 percent of patients and nine patients died. The majority of
serious adverse events and deaths were associated with advanced liver
disease.
“The ASTRAL study results demonstrate that a 12-week course of therapy
with the first fixed-dose combination of two pan-genotypic compounds can
provide high cure rates for patients with all HCV genotypes,” said
Norbert Bischofberger, Ph.D., Executive Vice President of Research and
Development and Chief Scientific Officer at Gilead. “We are pleased to
have now brought forward our second single tablet regimen for HCV
infection that complements Harvoni, our first single tablet regimen
approved specifically for patients with genotype 1 infection and which
could eliminate the need for HCV genotype testing. We look forward to
advancing the regulatory submissions for the SOF/VEL fixed-dose
combination.”
The U.S. Food and Drug Administration has assigned the SOF/VEL
fixed-dose combination a Breakthrough Therapy designation, which is
granted to investigational medicines that may offer major advances in
treatment over existing options.
The SOF/VEL fixed-dose combination is an investigational product and its
safety and efficacy have not yet been established.
About the ASTRAL Studies
The double-blind, placebo-controlled ASTRAL-1 trial enrolled 740
patients with chronic genotype 1, 2, 4, 5 or 6 HCV infection randomized
to SOF/VEL or placebo for 12 weeks.
The open-label ASTRAL-2 study evaluated the use of SOF/VEL or SOF+RBV
for 12 weeks in 266 genotype 2 HCV-infected patients.
The open-label ASTRAL-3 study evaluated the use of SOF/VEL for 12 weeks
or SOF+RBV for 24 weeks in 552 genotype 3 HCV-infected patients.
The ASTRAL-1 study met its primary endpoint of statistical superiority
to the pre-specified SVR12 goal of 85 percent (p<0.001). ASTRAL-2 and
ASTRAL-3 also met their respective endpoints. In ASTRAL-2, the SVR12
rate among genotype 2 HCV-infected patients receiving SOF/VEL for 12
weeks was statistically superior to the SVR12 rate for patients
receiving SOF+RBV for 12 weeks (p=0.018). In ASTRAL-3, the SVR12 rate
among genotype 3 HCV-infected patients receiving SOF/VEL for 12 weeks
was statistically superior to that of patients treated with SOF+RBV for
24 weeks (p<0.001).
The open-label ASTRAL-4 study evaluated the use of SOF/VEL with or
without RBV for 12 weeks and SOF/VEL for 24 weeks in 267 HCV-infected
patients with Child-Pugh class B cirrhosis, regardless of genotype.
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. Gilead has operations in more than 30
countries worldwide, with headquarters in Foster City, California.
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 Gilead may be unable to file for U.S. regulatory approval of the
SOF/VEL fixed-dose combination in the currently anticipated timelines.
In addition, the FDA and other regulatory agencies may not approve the
SOF/VEL fixed-dose combination, and any marketing approvals, if granted,
may have significant limitations on its use. 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 June 30, 2015, 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.
U.S. full Prescribing Information for Sovaldi and Harvoni are
available at www.gilead.com.
Sovaldi and Harvoni are registered trademarks of Gilead Sciences,
Inc. or its related companies.
For more information on Gilead Sciences, please visit the company’s
website at www.gilead.com,
follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000.
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