Sofosbuvir plus Velpatasvir for Chronic Pangenotypic HCV Infection: Phase III Results

November 17, 2015

Sofosbuvir plus Velpatasvir for Chronic Pangenotypic HCV Infection: Phase III Results

  1. Atif Zaman, MD, MPH

A universal treatment for chronic HCV infection may soon be available.

  1. Atif Zaman, MD, MPH

An experimental, once-daily pill for hepatitis C virus (HCV) leads to high rates of sustained virologic response across a wide range of patients, according to findings from four international, industry-supported, phase III trials reported below. The pill combines sofosbuvir (400 mg) with velpatasvir (100 mg; a novel pan-genotypic HCV NS5A inhibitor). The primary endpoint in all studies was sustained virologic response at 12 weeks after treatment ended (SVR12).

Some 700 patients with HCV genotypes 1, 2, 4, and 6 were randomized to receive sofosbuvir–velpatasvir or placebo for 12 weeks; an additional 35 patients with genotype 5 were assigned to active treatment (this genotype was relatively rare in the study regions). Roughly one third of patients had previously received HCV treatment, and nearly 20% had compensated cirrhosis. SVR12 was 99% with sofosbuvir–velpatasvir, with no differences according to genotype, prior treatment, or cirrhosis status. No placebo recipient had a sustained virologic response. Serious adverse events occurred in 2% of sofosbuvir–velpatasvir recipients (vs. 0% with placebo).

In a companion study, nearly 270 patients with HCV genotypes 1–6 (excluding 5) and decompensated cirrhosis were randomized to receive sofosbuvir–velpatasvir for 12 weeks, sofosbuvir–velpatasvir plus ribavirin for 12 weeks, or sofosbuvir–velpatasvir for 24 weeks. Rates of SVR12 were 83%, 94%, and 86%, respectively. Rates of serious adverse events ranged from 16% to 19%.

In two open-label studies, some 800 patients with HCV genotype 2 or 3 were randomly assigned to receive sofosbuvir–velpatasvir for 12 weeks or sofosbuvir plus ribavirin for 12 weeks (genotype 2) or 24 weeks (genotype 3). In patients with genotype 2 infection, rates of SVR12 were 99% vs. 94%, respectively (P=0.02), and virologic relapse rates were 0% vs. 5%, respectively. In patients with genotype 3 infection, SVR12 rates were 95% vs. 80%, respectively (P<0.001), and 89% vs. 58% in treatment-experienced patients with cirrhosis. Rates of serious adverse events in sofosbuvir–velpatasvir groups were ≤2%

In terms of safety, rates of discontinuation in the treatment groups in all studies were <3%. The most common side effects overall were fatigue, nausea, and headaches.

— Adapted from a Physician's First Watch article published on November 16, 2015.

Comment

These phase III results of the single-pill, once-daily, 12-week regimen of sofosbuvir plus velpatasvir demonstrated cure rates of about 90% or greater for all genotypes independent of previous treatment status or presence of compensated cirrhosis. Even among patients with decompensated cirrhosis, cure rates >90% can be achieved, and seemingly safely, in most genotypes with the addition of ribavirin to the regimen. The bar has yet again been raised, and we are one step closer to universal treatment of chronic HCV infection.

Editor Disclosures at Time of Publication

  • Disclosures for Atif Zaman, MD, MPH at time of publication Nothing to disclose

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