Date: 2014-11-11
Type of information: Presentation of results at a congress
phase: 2,3
Announcement: presentation of results at the 65th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting2014) in Boston
Company: Gilead Sciences (USA - CA)
Product: Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg)
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. Ledipasvir is a NS5A inhibitor. Harvoni® was approved by the FDA and Health Canada in October 2014 and is the first once-daily single tablet regimen for the treatment of chronic HCV genotype 1 infection in adults. Applications are pending in the European Union, Japan and New Zealand.
Disease: chronic hepatitis C
Therapeutic area: Infectious diseases
Country:
Trial details:
Latest
news: * On November 11, 2014, Gilead Sciences announced results from several Phase 2 and Phase 3 studies evaluating investigational uses of Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) for the treatment of chronic hepatitis C virus (HCV) infection in patients with limited or no treatment options, including patients with decompensated cirrhosis, patients with HCV recurrence following a liver transplant and patients who failed previous treatment with other direct acting antivirals. These data will be presented at the 65th Annual Meeting of the American Association for the Study of Liver Diseases in Boston. In a pooled analysis of Phase 2 and Phase 3 open-label studies (Oral #82) in more than 500 genotype 1 HCV infected patients with compensated cirrhosis who received Harvoni® alone or with ribavirin for 12 or 24 weeks, 96 percent of patients achieved sustained virologic response (SVR12). Patients who achieve SVR12 are considered cured of HCV infection. Two prospective analyses from a Phase 2 open-label study (Study GS-US-337-0123) evaluating patients with decompensated cirrhosis and those with HCV recurrence following liver transplantation also are being presented. In the first subgroup (Oral #239), 108 genotype 1 and 4 infected patients with decompensated cirrhosis, including those with moderate hepatic impairment (Child-Pugh-Turcotte (CPT) Class B) and severe hepatic impairment (CPT Class C), received Harvoni plus ribavirin for 12 or 24 weeks. Overall, SVR12 rates were 87 percent (n=45/52) in the 12-week arm and 89 percent (n=42/47) in the 24-week arm. The second subgroup (Oral #8) evaluated 12 or 24 weeks of Harvoni plus ribavirin among 223 genotype 1 and 4 patients who developed HCV recurrence following liver transplantation. Among non-cirrhotic patients, SVR12 rates were 96 percent (n=53/55) and 98 percent (n=55/56) following 12 and 24 weeks of treatment, respectively. For patients with compensated cirrhosis, SVR12 rates were 96 percent for both 12 weeks (n=25/26) and 24 weeks (n=24/25) of therapy. SVR12 rates among patients with decompensated cirrhosis were 81 percent for both 12 weeks (n=25/31) and 24 weeks (n=17/21) of therapy. Study GS-US-337-0121 (Late Breaker Oral #LB-6) evaluated 155 genotype 1 patients with compensated cirrhosis who had failed prior treatment with pegylated interferon (PegIFN)/ribavirin and subsequently PegIFN/ribavirinplus a protease inhibitor. In this study, patients were randomized (1:1) to receive Harvoni plus ribavirin for 12 weeks or Harvoni alone for 24 weeks. Ninety-six percent (n=74/77) of those receiving Harvoni plus ribavirin for 12 weeks and 97 percent (n=75/77) of those receiving Harvoni for 24 weeks achieved SVR12. In a second study (Oral #235), 51 genotype 1 patients who previously failed sofosbuvir/PegIFN/ribavirin, SOF/ribavirin or a sofosbuvir/ placebo/PegIFN/ribavirin treatment regimen received Harvoni® plus ribavirin for 12 weeks. Twenty-nine percent of study patients (n=15/51) had cirrhosis. Ninety-eight percent (n=50/51) achieved SVR12 following 12 weeks of treatment with Harvoni plus RBV. In all of these studies, Harvoni® was well tolerated and its safety profile was generally consistent with that observed in clinical trials of Harvoni. Adverse events included fatigue, headache, nausea and anemia, which was more common among patients taking ribavirin. Grade 3/4 laboratory abnormalities were infrequent and included decreases in hemoglobin, which is consistent with RBV-associated anemia. Most common (≥10 percent, all grades) adverse reactions were fatigue and headache.
