Gilead Announces SVR12 Rates From Three Phase 3 Studies Evaluating a Once-Daily Fixed-Dose Combination of Sofosbuvir and Ledipasvir for Genotype 1 Hepatitis C Patients
-- High Cure Rates Observed with Single Tablet Regimen May Eliminate
Interferon and Ribavirin from HCV Therapy for Genotype 1 Patients --
-- U.S. NDA Submission Planned for Q1 2014--
Foster City, CA, December 18, 2013 – 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 oncedaily
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.
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
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 eight, 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
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
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.
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