Results from two Phase 3 studies, FISSION and NEUTRINO, evaluating a 12-week course of the once-daily nucleotide Sofosbuvir in combination with Ribavirin ( FISSION ) and in combination with Ribavirin and Pegylated Interferon ( NEUTRINO ) among treatment-naïve patients with chronic hepatitis C virus ( HCV ) infection, were presented.
In the FISSION study, patients with genotype 2 or 3 HCV infection were randomized to receive either a 12-week course of Sofosbuvir plus Ribavirin ( RBV ) or standard of care with 24 weeks of Pegylated Interferon alfa-2a ( peg-IFN ) plus Ribavirin.
The study met its primary efficacy endpoint of non-inferiority of Sofosbuvir plus Ribavirin to Peg-Interferon plus Ribavirin, with 67% ( 170/253 ) of patients achieving a sustained virologic response ( SVR ) in the Sofosbuvir plus Ribavirin treatment group versus 67% ( 162/243 ) in the Peg-Interferon plus Ribavirin treatment group ( 95% CI for the difference: -7.5 to +8.0% for Sofosbuvir plus Ribavirin versus Peg-Interferon plus Ribavirin; predefined criterion for non-inferiority was a lower bound of a two sided 95 percent CI of 15% ).
All common adverse events ( greater than or equal to 10% in any group ) occurred more frequently in subjects receiving Peg-Interferon and Ribavirin as compared to Sofosbuvir and Ribavirin. The most common adverse events in the Sofosbuvir plus Ribavirin arm occurring in greater than or equal to 10% of the patients were fatigue, headache, nausea, insomnia and dizziness.
In the NEUTRINO study, patients with genotype 1, 4, 5 or 6 HCV infection were treated with a 12-week course of Sofosbuvir, RBV and Peg-Interferon.
This study met its primary efficacy endpoint of superiority compared to a predefined historic control SVR rate of 60% with 90% ( 295/327 ) of patients achieving SVR12 after completing therapy ( P less than 0.001 ).
The most common adverse events that occurred in greater than or equal to 20% of patients were fatigue, headache, nausea, insomnia and anemia.
In FISSION, treatment-naïve HCV genotype 2 and 3 patients were randomized ( 1:1 ) to receive either 12 weeks of Sofosbuvir 400 mg once daily plus Ribavirin ( 1,000 or 1,200 mg/day ) ( n=256 ) or 24 weeks of Peg-Interferon ( 180 microg/week ) plus Ribavirin ( 800 mg/day ) ( n=243 ).
Overall, 20% of patients had compensated cirrhosis and 72% had genotype 3 infection.
The SVR12 rates in patients receiving Sofosbuvir plus Ribavirin were 97% for genotype 2 patients and 56% for genotype 3 patients.
The SVR12 rates in patients receiving Peg-Interferon plus Ribavirin in this study were 78% for genotype 2 patients and 63% for genotype 3 patients.
Among patients with cirrhosis at baseline who received Sofosbuvir and Ribavirin, 47% achieved SVR12; 38% of cirrhotics who received Peg-Interferon plus Ribavirin achieved SVR12.
With the exception of one patient who was non-compliant, all patients in the Sofosbuvir and Ribavirin arm became HCV negative on treatment and relapse accounted for the virologic failures.
Three patients ( 1% ) receiving Sofosbuvir discontinued treatment due to adverse events compared to 26 patients ( 11% ) receiving Peg-Interferon and Ribavirin.
In NEUTRINO, 327 treatment-naïve HCV genotype 1, 4, 5 and 6 patients were treated for 12 weeks with Sofosbuvir 400 mg once daily in combination with Ribavirin ( 1,000 or 1,200 mg/day ) and Peg-Interferon ( 180 microg/week ).
Seventeen percent of patients had compensated cirrhosis and 89% were infected with genotype 1.
Among genotype 1 patients, 89% achieved SVR12. Of the 35 patients with genotypes 4, 5 or 6, 97% achieved SVR12.
Among patients with cirrhosis at baseline, 80% achieved SVR12.
All patients in this study became HCV RNA negative on treatment and relapse accounted for all virologic failures.
Five patients ( 2% ) receiving Sofosbuvir in combination with Peg-Interferon and Ribavirin discontinued treatment due to adverse events. ( Xagena )
Source: Gilead Sciences, 2013