The results from four Phase 3 clinical trials ( NEUTRINO, FISSION, POSITRON and FUSION ) evaluating Sofosbuvir ( Sovaldi ), an investigational once-daily nucleotide NS5B inhibitor for the treatment of chronic hepatitis C virus ( HCV ) infection, has been presented at the 48th Annual Meeting of the European Association for the Study of the Liver ( International Liver Congress 2013 ) in Amsterdam, The Netherlands.
In addition, detailed results from the four clinical studies have also been published in The New England Journal of Medicine ( NEJM ).
In the four trials, Sofosbuvir was administered to nearly 1,000 patients with chronic HCV infection as part of an all-oral 12-week or 16-week treatment regimen in combination with Ribavirin in genotypes 2 and 3, or with Ribavirin and Pegylated interferon ( peg-IFN ) for 12 weeks in genotypes 1, 4, 5 and 6.
Overall SVR12 rates ( sustained viral response 12 weeks after completing therapy ) from 50 to 90% were observed.
Patients who achieve SVR12 are considered cured of their HCV infection.
In the studies, Sofosbuvir-based HCV therapy has demonstrated high efficacy rates and a favorable safety profile while reducing the need for Interferon injections to 12 weeks, or eliminating Interferon completely from the regimen.
The NS5b region of the HCV viral genome for all patients who relapsed was sequenced and no S282T mutations were observed by population or deep sequencing ( 1% cutoff ).
There was no change in susceptibility to Sofosbuvir or Ribavirin observed by phenotypic analyses.
With the exception of one patient in FISSION who was non-compliant, relapse accounted for all virologic failures.
Adverse events were generally mild and included fatigue, nausea, headache, insomnia, pruritis, anemia and dizziness.
Less than 2% of patients in the Sofosbuvir treatment groups discontinued due to adverse events.
Sofosbuvir is a nucleotide analogue inhibitor of the HCV NS5B protein, which plays an essential role in HCV replication.
Sofosbuvir is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication. ( Xagena )
Source: Gilead Sciences, 2013