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Sofosbuvir plus GS-5816 appears to be a promising treatment regimen for treatment-naive patients with chronic genotype 1-6 hepatitis C virus infection without cirrhosis, according to a randomized, open-label study.
The work, led by Dr. Tram T. Tran, medical director of liver transplantation at Cedars-Sinai Medical Center in Los Angeles, found the drug combination achieved sustained viral response to treatment (SVR) rates of 77%-90% after 8 weeks and 91%-100% after 12 weeks.
Investigators enrolled 377 patients with genotype 1-6 HCV infection without cirrhosis in the study. Forty-seven percent were genotype 1; 33% were genotype 2; 14% were genotype 3; 4% were genotype 4; less than 1% were genotype 5; and 2% were genotype 6.
During the first part of the study, 154 patients were randomized to receive either sofosbuvir (SOF) and 25 mg of GS-5816, or SOF and 100 mg of GS-5816, for 12 weeks. In the second part, 223 patients with genotype 1 and 2 hepatitis C without cirrhosis who had not received prior treatment were randomized to one of the following four treatments for 8 weeks: SOF and 25 mg of GS-5816; SOF, 25 mg of GS-5816, and ribavirin; SOF and 100 mg of GS-5816; or SOF, 100 mg of GS-5816, and ribavirin. SOF was dosed at 400 mg; ribavirin was administered as 1,000 mg-1,200 mg in a divided daily dose.
SVR rates at 12 weeks in the first part of the study, with 12 weeks of treatment, were 96% using the 25-mg dose of GS-5816 and 100% with the 100-mg dose in patients with genotype 1 HCV infection, Dr. Tran said at the annual meeting of the American Association for the Study of Liver Diseases. For patients with genotype 2, SVR rates at 12 weeks were 91% and 100% with the 25-mg and 100-mg doses, respectively. SVR rates at 12 weeks for the other genotypes ranged from 86% to 100%.
In the second part of this study that reduced treatment duration to 8 weeks and added ribavirin to some treatment arms, SVR rates at 12 weeks ranged from 81% to 90% for patients with genotype 1 infection and from 77% to 88% for patients with genotype 2 infection.
The most frequently reported adverse events were fatigue, headache,and nausea, occurring in more than 10% of patients. One patient discontinued treatment because of abdominal pain.
“SVR rates were lower and relapse rates increased in patients with genotype 1 or 2 infection when treated for 8 weeks instead of 12 weeks,” Dr. Tran said.
A coformulated, fixed dose of 400 mg SOF and 100 mg of GS-5816 is now in a phase 3 clinical trial, she said.
Sofosbuvir plus GS-5816 appears to be a promising treatment regimen for treatment-naive patients with chronic genotype 1-6 hepatitis C virus infection without cirrhosis, according to a randomized, open-label study.
The work, led by Dr. Tram T. Tran, medical director of liver transplantation at Cedars-Sinai Medical Center in Los Angeles, found the drug combination achieved sustained viral response to treatment (SVR) rates of 77%-90% after 8 weeks and 91%-100% after 12 weeks.
Investigators enrolled 377 patients with genotype 1-6 HCV infection without cirrhosis in the study. Forty-seven percent were genotype 1; 33% were genotype 2; 14% were genotype 3; 4% were genotype 4; less than 1% were genotype 5; and 2% were genotype 6.
During the first part of the study, 154 patients were randomized to receive either sofosbuvir (SOF) and 25 mg of GS-5816, or SOF and 100 mg of GS-5816, for 12 weeks. In the second part, 223 patients with genotype 1 and 2 hepatitis C without cirrhosis who had not received prior treatment were randomized to one of the following four treatments for 8 weeks: SOF and 25 mg of GS-5816; SOF, 25 mg of GS-5816, and ribavirin; SOF and 100 mg of GS-5816; or SOF, 100 mg of GS-5816, and ribavirin. SOF was dosed at 400 mg; ribavirin was administered as 1,000 mg-1,200 mg in a divided daily dose.
SVR rates at 12 weeks in the first part of the study, with 12 weeks of treatment, were 96% using the 25-mg dose of GS-5816 and 100% with the 100-mg dose in patients with genotype 1 HCV infection, Dr. Tran said at the annual meeting of the American Association for the Study of Liver Diseases. For patients with genotype 2, SVR rates at 12 weeks were 91% and 100% with the 25-mg and 100-mg doses, respectively. SVR rates at 12 weeks for the other genotypes ranged from 86% to 100%.
In the second part of this study that reduced treatment duration to 8 weeks and added ribavirin to some treatment arms, SVR rates at 12 weeks ranged from 81% to 90% for patients with genotype 1 infection and from 77% to 88% for patients with genotype 2 infection.
The most frequently reported adverse events were fatigue, headache,and nausea, occurring in more than 10% of patients. One patient discontinued treatment because of abdominal pain.
“SVR rates were lower and relapse rates increased in patients with genotype 1 or 2 infection when treated for 8 weeks instead of 12 weeks,” Dr. Tran said.
A coformulated, fixed dose of 400 mg SOF and 100 mg of GS-5816 is now in a phase 3 clinical trial, she said.
Sofosbuvir plus GS-5816 appears to be a promising treatment regimen for treatment-naive patients with chronic genotype 1-6 hepatitis C virus infection without cirrhosis, according to a randomized, open-label study.
The work, led by Dr. Tram T. Tran, medical director of liver transplantation at Cedars-Sinai Medical Center in Los Angeles, found the drug combination achieved sustained viral response to treatment (SVR) rates of 77%-90% after 8 weeks and 91%-100% after 12 weeks.
Investigators enrolled 377 patients with genotype 1-6 HCV infection without cirrhosis in the study. Forty-seven percent were genotype 1; 33% were genotype 2; 14% were genotype 3; 4% were genotype 4; less than 1% were genotype 5; and 2% were genotype 6.
During the first part of the study, 154 patients were randomized to receive either sofosbuvir (SOF) and 25 mg of GS-5816, or SOF and 100 mg of GS-5816, for 12 weeks. In the second part, 223 patients with genotype 1 and 2 hepatitis C without cirrhosis who had not received prior treatment were randomized to one of the following four treatments for 8 weeks: SOF and 25 mg of GS-5816; SOF, 25 mg of GS-5816, and ribavirin; SOF and 100 mg of GS-5816; or SOF, 100 mg of GS-5816, and ribavirin. SOF was dosed at 400 mg; ribavirin was administered as 1,000 mg-1,200 mg in a divided daily dose.
SVR rates at 12 weeks in the first part of the study, with 12 weeks of treatment, were 96% using the 25-mg dose of GS-5816 and 100% with the 100-mg dose in patients with genotype 1 HCV infection, Dr. Tran said at the annual meeting of the American Association for the Study of Liver Diseases. For patients with genotype 2, SVR rates at 12 weeks were 91% and 100% with the 25-mg and 100-mg doses, respectively. SVR rates at 12 weeks for the other genotypes ranged from 86% to 100%.
In the second part of this study that reduced treatment duration to 8 weeks and added ribavirin to some treatment arms, SVR rates at 12 weeks ranged from 81% to 90% for patients with genotype 1 infection and from 77% to 88% for patients with genotype 2 infection.
The most frequently reported adverse events were fatigue, headache,and nausea, occurring in more than 10% of patients. One patient discontinued treatment because of abdominal pain.
“SVR rates were lower and relapse rates increased in patients with genotype 1 or 2 infection when treated for 8 weeks instead of 12 weeks,” Dr. Tran said.
A coformulated, fixed dose of 400 mg SOF and 100 mg of GS-5816 is now in a phase 3 clinical trial, she said.
FROM THE LIVER MEETING 2014
Key clinical point: Sofosbuvir plus GS-5816 was well tolerated and achieved high SVR12 rates among treatment-naive patients with chronic genotype 1-6 HCV infection without cirrhosis.
Major finding: SVR rates ranged from 77% to 90% with 8 weeks of treatment and from 91% to 100% with 12 weeks of treatment.
Data source: A phase II study including evaluation of sofosbuvir plus GS-5816 with or without ribavirin in 377 treatment-naive patients with chronic genotype 1-6 HCV infection without cirrhosis.
Disclosures: The trial was sponsored by Gilead Sciences, manufacturer of sofosbuvir and GS-5816. Dr. Tan has received consulting and speaker fees from Gilead and served on an advisory committee for the company, and has received fees from Bristol-Myers Squibb, AbbVie and Janssen. Most coauthors also received fees from Gilead and other manufacturers; five are Gilead employees.
