When DAA Treatment for Hepatitis C Fails, 3-Drug Regimen "Highly Effective"

By Kelly Young

Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, DFASAM

The combination of sofosbuvir, velpatasvir, and voxilaprevir is effective for hepatitis C in patients with virologic failure after direct-acting antiviral agent (DAA) treatment, according to two phase 3, industry-funded trials in the New England Journal of Medicine.

For POLARIS-1, roughly 300 patients with genotype-1 hepatitis C infection whose prior NS5A-inhibitor treatment had failed were randomized to either daily sofosbuvir-velpatasvir-voxilaprevir or placebo for 12 weeks. An additional 100 patients with non-genotype 1 infection were enrolled in the treatment group.

For POLARIS-4, over 300 patients with hepatitis C who had taken a direct-acting antiviral other than an NS5A inhibitor were randomized to receive sofosbuvir-velpatasvir with or without voxilaprevir.

Sustained virologic response 12 weeks after treatment ended was 96% for the POLARIS-1 treatment group (vs. 0% with placebo). In POLARIS-4, the three-drug regimen had a 98% response rate, compared with 90% for sofosbuvir-velpatasvir. Sustained response rates were high for all genotypes.

Infectious disease expert Dr. Paul Sax comments: "This triple-therapy treatment strategy provides a highly effective option for that small proportion of patients who failed prior treatment for hepatitis C with non-interferon-based regimens. Although few in number, candidates for this treatment (and their clinicians) will welcome this treatment when it is FDA approved."