Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need.
Dr Nezam Afdhal and colleagues conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor.
Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet for 12 weeks, ledipasvir–sofosbuvir plus ribavirin for 12 weeks, ledipasvir–sofosbuvir for 24 weeks, or ledipasvir–sofosbuvir plus ribavirin for 24 weeks.
The team's primary end point was a sustained virologic response at 12 weeks after the end of therapy.
|Rates of sustained virologic response were 94% in the group that received 12 weeks of ledipasvir–sofosbuvir|
|New England Journal of Medicine|
Among the 440 patients who underwent randomization and were treated, 20% had cirrhosis and 79% had HCV genotype 1a infection.
The team found that the rates of sustained virologic response were high in all treatment groups, with 94% in the group that received 12 weeks of ledipasvir–sofosbuvir, 96% in the group that received 12 weeks of ledipasvir–sofosbuvir and ribavirin, 99% in the group that received 24 weeks of ledipasvir–sofosbuvir, and 99% in the group that received 24 weeks of ledipasvir–sofosbuvir and ribavirin.
The researchers observed that no patient discontinued treatment owing to an adverse event.
The most common adverse events were fatigue, headache, and nausea.
Dr Afdhal's team commented, "Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment."