New Hepatitis C Combination Pill Targets Hard-to-Treat Patients

A new pill that combines three antiviral drugs was almost 100% effective in curing hepatitis C in patients who have failed to respond to other treatments, an international team of researchers reported in the New England Journal of Medicine.

The once-a-day medication consists of direct-acting antiviral (DAA) sofosbuvir (Sovaldi/Gilead Sciences Inc.) along with voxilaprevir and velpatasvir. Velpatasvir, an NS5A inhibitor that reduces the ability of the hepatitis C virus to replicate, also is used with sofosbuvir in a two-drug Gilead product that’s marketed as Epclusa.

“Sofosbuvir—velpatasvir–voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed,” the team concluded in the article published on June 1.

Today’s DAA drugs can already cure more than 90% of patients with liver-attacking hepatitis C. But a small percentage don’t respond to antiviral treatments. The researchers noted that while the percentage of these failures is relatively small, the overall number of patients who remain infected after DAA therapy is significant because 150 million people worldwide are estimated to carry the virus.

Currently there are no approved retreatment options for people who don’t respond to a regimen containing an NS5A inhibitor, the researchers said. These are the patients who comprise most recent failures, they said.

To try to reach this group, lead researcher Dr. Marc Bourlière at the Hospital Saint Joseph in Marseilles, France, and others across the US, Canada and elsewhere, conducted two international trials.

In the first, 300 patients, all with hepatitis C genotype 1, were randomly given either the new combination pill or a placebo. In addition, 114 people with other genotypes took the combination drug. They all received the medication daily for 12 weeks.

The researchers found that 96% of patients who took the combination pill responded to the treatment. There was zero response among the placebo-takers.

In the second trial, the team targeted 314 patients with genotypes 1, 2 or 3. All had failed previous treatments, but hadn't been given a NS5A inhibitor, such as velpatasvir. This group received either the triple combination pill or a mix of sofosbuvir and velpatasvir. In addition, 19 patients with genotype 4 took the triple combination drug.

At the end of this 12-week trial, 98% of the patients who were given the new triple combination pill responded. The sofosbuvir-velpatasvir group saw a 90% response rate.

The researchers cautioned that the small number of patients they studied in some rarer genotypes may limit the ability to generalize results to these groups. The findings also cannot be generalized to patients who were excluded from the trials, such as those coinfected with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) and those with decompensated cirrhosis.

The study was supported by Gilead. Bourlière reported receiving grant funding, consulting and lecture fees, and payment for serving on an advisory board from Gilead, Merck Sharp & Dohme and AbbVie. He also reported receiving consulting, lecture and advisory board fees from Janssen and Bristol-Myers Squibb; meeting fees were paid for by Genfit and Intercept Pharmaceuticals Inc.

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