Date: 2014-11-11
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the 65th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting® 2014) in Boston.
Company: Gilead Sciences (USA - CA)
Product: sofosbuvir and velpatasvir (GS-5816)
Action
mechanism: direct-acting antiviral agent/nucleotide analog. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. This direct-acting agent interferes directly with the HCV life cycle by suppressing viral replication. GS-5816 is a second-generation investigational NS5A inhibitor.
Disease: chronic hepatitis C virus infection
Therapeutic area: Infectious diseases
Country:
Trial details:
Latest
news: * On November 11, 2014, Gilead Sciences announced data from three Phase 2 open-label studies evaluating the safety and efficacy of an investigational all-oral pan-genotypic regimen containing the nucleotide analog polymerase inhibitor sofosbuvir, approved as Sovaldi® by the FDA in December 2013, and the investigational NS5A inhibitor GS-5816 for the treatment of chronic hepatitis C virus (HCV) infection. These data are being presented this week at the 65th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting® 2014) in Boston. All three studies evaluated sofosbuvir 400 mg plus GS-5816 25 or 100 mg, with and without ribavirin, for eight or 12 weeks. Rates of sustained virologic response (SVR12) ranged from 88 percent to 100 percent among those receiving sofosbuvir plus GS-5816 100 mg for 12 weeks – the regimen selected for Phase 3 studies. Patients who achieve SVR12 are considered cured of HCV infection. The first study, GS-US-342-0109 (Oral #197), evaluated 12 weeks of sofosbuvir plus GS-5816 with and without ribavirin in treatment-experienced genotype 1 and 3 patients with and without cirrhosis. The genotype 1 patients had all failed a prior treatment course that included a protease inhibitor. The number and proportion of patients achieving SVR12 are summarized in the table below. SVR12 Rates Among Treatment-Experienced Patients in Study GS-US-342-0109 GT1 cirrhosis GT1 cirrhosis GT3 cirrhosis GT3 cirrhosis The second study, ELECTRON 2 , evaluated the same combination of sofosbuvir plus GS-5816, with and without ribavirine, for eight weeks in non-cirrhotic, treatment-naïve genotype 3 patients. Patients receiving sofosbuvir with GS-5816 100 mg achieved SVR12 rates of 100 percent (n=26/26) with RBV and 96 percent (n=26/27) without RBV. The third study, GS-US-342-0102, evaluated sofosbuvir plus GS-5816, with and without ribavirine, among non-cirrhotic treatment-naïve patients. The results of Part A of the study evaluating 12 weeks of therapy were presented at the 49th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress 2014) in April 2014. The results of Part B, presented at the Liver Meeting, evaluated eight weeks of sofosbuvir plus GS-5816, with and without ribavirine, in patients with genotype 1 or 2 HCV infection. Among genotype 1 patients receiving sofosbuvir plus GS-5816 100 mg, SVR12 rates were 81 percent (n=25/31) and 90 percent (n=26/29), with and without ribavirine, respectively. Genotype 2 patients achieved SVR12 rates of 88 percent (n=23/26) with ribavirine and 88 percent (n=23/26) without ribavirine. Sofosbuvir plus GS-5816 was well tolerated in over 800 patients with HCV infection evaluated in these three studies. There was a low incidence of serious adverse effects and few discontinuations due to adverse events. The most frequently reported adverse events (>10%) were fatigue, headache, nausea and insomnia. The most frequently observed hematologic abnormality was hemoglobin decrease in the ribavirine-containing treatment groups. Regimen
without
with
without
withSOF+GS-5816 100 mg 100% (n=20/20) 100% (n=7/7) 100% (n=27/27) 88% (n=23/26) SOF+GS-5816 100 mg +RBV 100% (n=18/18) 90% (n=9/10) 100% (n=26/26) 96% (n=25/26)
