Gilead Sciences, Inc. (Nasdaq: GILD) today 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 this week at the 65th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2014) in Boston.
“Chronic hepatitis C patients with advanced liver disease are among the most difficult to cure and traditionally have had limited or no treatment options,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. “The data presented this week demonstrate that provides high cure rates for patients with advanced liver disease, as well as for those who failed prior treatment with other antivirals, including sofosbuvir-based regimens.”
Ledipasvir/sofosbuvir was approved by the U.S. Food and Drug Administration on October 10, 20141 and Health Canada on October 16, 2014 under the trade name Harvoni and is the first once-daily single tablet regimen for the treatment of chronic hepatitis C genotype 1 infection in adults. Applications are pending in the European Union, Japan and Switzerland.
Advanced Liver Disease
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 ledipasvir/sofosbuvir alone or with ribavirin (RBV) for 12 or 24 weeks, 96 percent of patients achieved sustained virologic response (SVR12). Patients who achieve SVR12 are considered cured of HCV infection.2
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 ledipasvir/sofosbuvir plus RBV for 12 or 24 weeks.3 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 ledipasvir/sofosbuvir plus RBV among 223 genotype 1 and 4 patients who developed HCV recurrence following liver transplantation.4 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.
Retreatment of Patients Who Failed Prior 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)/RBV and subsequently PegIFN/RBV plus a protease inhibitor. In this study, patients were randomized (1:1) to receive ledipasvir/sofosbuvir plus RBV for 12 weeks or ledipasvir/sofosbuvir alone for 24 weeks. Ninety six percent (n=74/77) of those receiving ledipasvir/sofosbuvir plus RBV for 12 weeks and 97 percent (n=75/77) of those receiving ledipasvir/sofosbuvir for 24 weeks achieved SVR12.5
In a second study (Oral #235), 51 genotype 1 patients who previously failed SOF/PegIFN/RBV, SOF/RBV or a SOF placebo/PegIFN/RBV treatment regimen received ledipasvir/sofosbuvir plus RBV for 12 weeks. Twenty nine percent (n=15/51) had cirrhosis.6 Ninety eight percent (n=50/51) achieved SVR12 following 12 weeks of treatment with ledipasvir/sofosbuvir plus RBV.
In all of these studies, ledipasvir/sofosbuvir was well tolerated and its safety profile was generally consistent with that observed in clinical trials of ledipasvir/sofosbuvir. Adverse events included fatigue, headache, nausea and anemia, which was more common among patients taking RBV. Grade 3/4 laboratory abnormalities were infrequent and included decreases in hemoglobin, which is consistent with RBV-associated anemia.
The safety and efficacy of ledipasvir/sofosbuvir have not been established for the investigational uses described above.
