Gilead Issues SVR12 Rates from Three Phase 3 STudies, Says Ion-1 Rate 97.7%, NDA Submission Planned for Q1'14

Gilead Sciences, Inc.

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.         Study   Population   Treatment   Duration   SVR12 Rates SOF/LDV   12 weeks   97.7% GT 1 treatment-naïve (209/214) ION-1 SOF/LDV + RBV   12 weeks   97.2% (including 15.7 percent (211/217) (136/865) with cirrhosis) SOF/LDV   24 weeks   NA (n=217)     SOF/LDV + RBV   24 weeks   NA (n=217) SOF/LDV   12 weeks   93.6% (102/109) GT 1 treatment-experienced SOF/LDV+RBV   12 weeks   96.4% ION-2 (107/111) (including 20.0 percent SOF/LDV   24 weeks   99.1% (88/440) with cirrhosis) (108/109)     SOF/LDV+RBV   24 weeks   99.1% (110/111) SOF/LDV   8 weeks   94.0% (202/215) ION-3 GT 1 treatment-naïve SOF/LDV + RBV   8 weeks   93.1% (201/216)     SOF/LDV   12 weeks   95.4% (206/216)   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.