Sustained Virologic Response With Sofosbuvir in Hepatitis C Patients
Phase III trial evaluates drug in patients unwilling or unable to take interferon (Nov. 27)
Results have been reported from the phase III POSITRON study, which evaluated a 12-week course of once-daily sofosbuvir (formerly GS-7977, Gilead Sciences) plus ribavirin (RBV) in patients with genotype 2 or 3 chronic hepatitis C virus (HCV) infection who are not candidates for treatment with interferon (IFN). The study found that 78% of patients (161/207) had undetectable HCV RNA 12 weeks after completing therapy (SVR12).
In the POSITRON trial, HCV genotype 2 or 3 patients who were interferon intolerant, interferon ineligible, or unwilling to take IFN were randomly assigned to receive 12 weeks of treatment with either sofosbuvir 400 mg once daily plus weight-based RBV twice daily (n = 207) or matching placebo (n = 71). Of the 207 patients in the sofosbuvir/RBV arm, 15% had compensated cirrhosis (more advanced liver disease), and 53% were infected with HCV genotype 2.
SVR12 rates were 93% in genotype 2 patients and 61% in genotype 3 patients. In the small proportion of patients with cirrhosis at baseline who received sofosbuvir/RBV, 61% achieved SVR12. All patients receiving sofosbuvir/RBV became HCV RNA negative during treatment, and relapse accounted for all virologic failures. No patient in the placebo group achieved SVR12. The most common adverse events reported in greater than 10% of patients in the study were fatigue, nausea, headache, insomnia, pruritis, and anemia.
The phase III clinical trial program for sofosbuvir includes two additional studies that are evaluating 12 and 16 weeks of therapy with sofosbuvir plus RBV in patients infected with HCV genotype 2 or 3. A fourth phase III trial is evaluating sofosbuvir combined with RBV and peg-IFN among patients with HCV genotypes 1, 4, 5, and 6. These studies will support initial regulatory filings in mid-2013 for an all-oral therapy with sofosbuvir plus RBV among genotype 2 or 3 treatment-naïve, treatment-experienced, and interferon-intolerant patients, and for sofosbuvir in combination with RBV and peg-IFN among treatment-naïve patients with HCV genotypes 1, 4, 5, and 6.
Sofosbuvir is a once-daily nucleotide analog polymerase inhibitor.
Source: Gilead Sciences; November 27, 2012.