In phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor Sofosbuvir and the NS5A inhibitor Ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus ( HCV ) genotype 1 infection.
Researchers have conducted a phase 3, open-label study involving previously untreated patients with chronic HCV genotype 1 infection.
Patients were randomly assigned in a 1:1:1:1 ratio to receive Ledipasvir and Sofosbuvir in a fixed-dose combination tablet once daily for 12 weeks, Ledipasvir - Sofosbuvir plus Ribavirin for 12 weeks, Ledipasvir -Sofosbuvir for 24 weeks, or Ledipasvir - Sofosbuvir plus Ribavirin for 24 weeks.
The primary endpoint was a sustained virologic response at 12 weeks after the end of therapy.
Of the 865 patients who underwent randomization and were treated, 16% had cirrhosis, 12% were black, and 67% had HCV genotype 1a infection.
The rates of sustained virologic response were 99% ( 95% confidence interval [CI], 96 to 100 ) in the group that received 12 weeks of Ledipasvir - Sofosbuvir; 97% ( 95% CI, 94 to 99 ) in the group that received 12 weeks of Ledipasvir - Sofosbuvir plus Ribavirin; 98% ( 95% CI, 95 to 99 ) in the group that received 24 weeks of Ledipasvir - Sofosbuvir; and 99% ( 95% CI, 97 to 100 ) in the group that received 24 weeks of Ledipasvir - Sofosbuvir plus Ribavirin.
No patient in either 12-week group discontinued Ledipasvir - Sofosbuvir owing to an adverse event.
The most common adverse events were fatigue, headache, insomnia, and nausea.
In conclusion, once-daily Ledipasvir - Sofosbuvir with or without Ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection. ( Xagena )
Afdhal N et al, NEJM 2014; Epub ahead of print