Gilead Sciences, Inc. (Nasdaq: GILD) today announced topline results
from three Phase 3 clinical trials (ION-1, ION-2 and ION-3) evaluating
the investigational once-daily fixed-dose combination of the nucleotide
analog polymerase inhibitor sofosbuvir (SOF) 400 mg and the NS5A
inhibitor ledipasvir (LDV) 90 mg, with and without ribavirin (RBV), for
the treatment of genotype 1 chronic hepatitis C virus (HCV) infection.
Across the three studies, 1,952 patients with genotype 1 HCV infection
were randomized to receive SOF/LDV with or without RBV for eight, 12 or
24 weeks of therapy. Of these, 1,512 patients were treatment-naïve, 440
were treatment experienced and 224 had compensated cirrhosis.
The intent-to-treat SVR12 rates observed to date in the ION studies are
summarized in the table below. Results of the 24-week arms from ION-1
will be available in the first quarter of 2014 and will be presented at
a future scientific meeting.
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Study
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Population
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Treatment
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Duration
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SVR12 Rates
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ION-1
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GT 1 treatment-naïve
(including 15.7 percent (136/865) with cirrhosis)
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SOF/LDV
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12 weeks
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97.7% (209/214)
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SOF/LDV + RBV
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12 weeks
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97.2% (211/217)
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SOF/LDV
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24 weeks
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NA (n=217)
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SOF/LDV + RBV
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24 weeks
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NA (n=217)
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ION-2
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GT 1 treatment-experienced
(including 20.0 percent (88/440) with cirrhosis)
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SOF/LDV
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12 weeks
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93.6% (102/109)
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SOF/LDV+RBV
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12 weeks
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96.4% (107/111)
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SOF/LDV
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24 weeks
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99.1% (108/109)
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SOF/LDV+RBV
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24 weeks
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99.1% (110/111)
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ION-3
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GT 1 treatment-naïve
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SOF/LDV
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8 weeks
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94.0% (202/215)
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SOF/LDV + RBV
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8 weeks
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93.1% (201/216)
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SOF/LDV
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12 weeks
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95.4% (206/216)
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Of the 1,518 patients randomized to the 12-week arms of ION-1 and to all
arms of ION-2 and ION-3, 1,456 patients (95.9 percent) achieved the
primary efficacy endpoint of SVR12. Of the 62 patients (4.1 percent) who
failed to achieve SVR12, 36 patients (2.4 percent) experienced virologic
failure: 35 due to relapse and only one patient due to on-treatment
breakthrough (with documented non-compliance). Twenty-six patients (1.7
percent) were lost to follow-up or withdrew consent.
Fewer adverse events were observed in the RBV-free, fixed-dose
combination arms compared to the RBV-containing arms in all ION studies.
Adverse events observed in those taking the SOF/LDV tablet were
generally mild and included fatigue and headache. In the RBV-containing
arms of the ION studies, the most common adverse events were fatigue,
headache, nausea and insomnia. Anemia, which is a common side effect
associated with RBV, was reported in 0.5 percent of patients in the
SOF/LDV arms versus 9.2 percent of patients in the RBV-containing arms.
Less than 1 percent of patients in the studies discontinued treatment
due to treatment-emergent adverse events.
“The results of the ION studies demonstrate that a simple, safe and
short course of therapy with a single tablet regimen of
sofosbuvir/ledipasvir can provide high cure rates among patients with
genotype 1 HCV infection, while eliminating the need for both interferon
and ribavirin,” said Norbert Bischofberger, PhD, Executive Vice
President of Research and Development and Chief Scientific Officer.
“With the availability of these results, Gilead is finalizing its
regulatory filing for sofosbuvir/ledipasvir, with the goal of submitting
a New Drug Application in the first quarter of 2014.”
The FDA has assigned the SOF/LDV fixed-dose combination a Breakthrough
Therapy designation, which is granted to investigational medicines that
may offer major advances in treatment over existing options. Sofosbuvir
was approved as Sovaldi™ in the United States on December 6 and in
Canada on December 13. Applications are pending in the European Union,
Australia and New Zealand, Switzerland and Turkey.
About the ION Studies
The Phase 3 ION studies are randomized, open-label Phase 3 clinical
trials evaluating the efficacy and safety of a once-daily fixed-dose
combination of SOF/LDV for 8, 12 or 24 weeks, with and without RBV,
among 1,952 genotype 1 HCV patients. The studies included patients who
were treatment-naïve or who had failed previous treatment, including
protease inhibitor-based regimens. The primary endpoint for each study
was SVR12. Complete results from all three studies will be presented at
a future scientific conference.
In ION-1, 865 treatment-naïve genotype 1 HCV patients, including those
with cirrhosis, received SOF/LDV with or without RBV for 12 or 24 weeks.
In March 2013, a planned review by the study’s Data and Safety
Monitoring Board (DSMB) of interim safety and efficacy data from an
initial enrollment of patients concluded that the trial should continue
without modification. Enrollment of the remaining patients was completed
in May 2013. Prior to the DSMB meeting, the statistical analysis plan
was amended to allow for the analysis of the primary efficacy endpoint
for the two 12-week arms, independent of the 24-week arms. Per the
amendment, if SVR12 rates in the 12-week arms were >90 percent
(including among those with cirrhosis), early regulatory filings could
be pursued, given that longer treatment durations would not be able to
show statistically significantly higher SVR12 rates.
The ION-2 study evaluated 440 treatment-experienced genotype 1 HCV
patients who had failed past therapy with regimens containing Peg-IFN
(including Peg-IFN plus a protease inhibitor). Patients received SOF/LDV
with or without RBV for 12 or 24 weeks.
In ION-3, 647 non-cirrhotic treatment-naïve genotype 1 HCV patients
received SOF/LDV with or without RBV for 8 weeks or without RBV for 12
weeks.
The SOF/LDV fixed-dose combination is an investigational product and its
safety and efficacy has not yet been established.
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 and South America, Europe and
Asia Pacific.
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/LDV fixed-dose combination in the currently anticipated timelines.
In addition, the FDA and other regulatory agencies may not approve the
SOF/LDV fixed-dose combination, and any marketing approvals, if granted,
may have significant limitations on its use. Additional clinical studies
of sofosbuvir and the SOF/LDV fixed-dose combination, including results
from the 24-week arms of ION-1, may not produce favorable results. As a
result, Gilead may not be able to successfully commercialize the SOF/LDV
fixed-dose combination, and may make a strategic decision to discontinue
its development if, for example, the market for the product fails to
materialize as expected. 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 September 30, 2013, 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 is available at www.Sovaldi.com.
Sovaldi is a trademark 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.
Copyright Business Wire 2013