Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents have limited retreatment options.
Dr Marc Bourličre and colleagues conducted two phase 3 trials involving patients who had been previously treated with a direct-acting antiviral agents-containing regimen.
In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir or matching placebo once daily for 12 weeks.
The team enrolled patients who were infected with HCV of other genotypes in the sofosbuvir–velpatasvir–voxilaprevir group.
|The rate of response was 98% with sofosbuvir–velpatasvir–voxilaprevir|
|New England Journal of Medicine|
In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a direct-acting antiviral agents regimen but not an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive sofosbuvir–velpatasvir–voxilaprevir or sofosbuvir–velpatasvir for 12 weeks.
An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir–velpatasvir–voxilaprevir group.
In the 3 active-treatment groups, 46% of the patients had compensated cirrhosis.
In POLARIS-1, the team found that the rate of sustained virologic response was 96% with sofosbuvir–velpatasvir–voxilaprevir, as compared with 0% with placebo.
In POLARIS-4, the research team noted that the rate of response was 98% with sofosbuvir–velpatasvir–voxilaprevir, and 90% with sofosbuvir–velpatasvir.
The most common adverse events were headache, fatigue, diarrhea, and nausea.
In the active-treatment groups in both trials, the percentage of patients who discontinued treatment owing to adverse events was 1% or lower.
Dr Bourličre's team comments, "Sofosbuvir–velpatasvir–voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a direct-acting antiviral agents regimen had previously failed."