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.
Dr Nezam Afdhal and colleagues conducted a phase 3, open-label study involving previously untreated patients with chronic HCV genotype 1 infection.
Patients were randomly assigned 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 end point was a sustained virologic response at 12 weeks after the end of therapy.
|Rates of sustained virologic response were 99% in the group that received 12 weeks of ledipasvir–sofosbuvir|
|New England Journal of Medicine|
Of the 865 patients who underwent randomization and were treated, 16% had cirrhosis, 12% were black, and 67% had HCV genotype 1a infection.
The team found that the rates of sustained virologic response were 99% in the group that received 12 weeks of ledipasvir–sofosbuvir, and 97% in the group that received 12 weeks of ledipasvir–sofosbuvir plus ribavirin.
The researchers noted that rates of sustained virologic response were 98% in the group that received 24 weeks of ledipasvir–sofosbuvir, and 99% 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.
Dr Afdhal's team concludes, "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."