EASL 2012 Additional data from a Merck-sponsored clinical trial help clarify the efficacy of Victrelis (boceprevir) combined with pegylated interferon and ribavirin (peg-IFN/RBV) in people with genotype 1 hepatitis C virus (HCV) infection who were null responders to previous peg-IFN/RBV treatment. The latest results from the PROVIDE clinical trial were presented by Jean-Pierre Bronowicki, MD, PhD, of the Centre Hospitalier Universitaire de Nancy-Brabois in  Vandoeuvre-lès-Nancy, France, and his colleagues at the 47th Annual Meeting of the European Association for the Study of the Liver (EASL) in Barcelona.

PROVIDE has been closely watched by hepatitis C care providers because little is known about Victrelis’s effectiveness in null responders—those who experienced minimal HCV viral load reductions while undergoing treatment with peg-IFN/RBV.
RESPOND-2, one of the key clinical trials designed to test Victrelis’s efficacy in treatment-experienced people living with genotype 1 HCV infection before the drug’s approval, only included people who had prior relapsing infection or prior partial responses to earlier therapy—prior null responders were not included in the trial.

To address this important knowledge gap, the PROVIDE study has enrolled people living with genotype 1 HCV infection who were null responders, partial responders or relapsers while receiving peg-IFN/RBV—without Victrelis—in previous Phase II or III clinical trials conducted by Merck. Of the 168 volunteers enrolled in PROVIDE, 50 met the definition for null response (an HCV viral load that didn’t drop by at least 2 log during the first 12 weeks of treatment).

Once enrolled in PROVIDE, all study volunteers received a four-week course of peg-IFN plus weight-based dosing of RBV. From there, standard doses of Victrelis (800 mg three times daily) were added to peg-IFN/RBV for an additional 44 weeks.

Sixty-seven percent of the PROVIDE subjects were male, and 84 percent were white. The average age upon study entry was 52 years. More than three quarters of the patients had high HCV viral loads (in excess of 800,000); 10 percent had cirrhosis; and 61 percent had genotype 1a HCV infection.

Four patients in the study discontinued pre-IFN/RBV before adding Victrelis at week four—three patients were prior null responders and one was a prior partial responders/relapser.

The sustained virologic response rate at week 24 (SVR 24)—the percentage of people believed to be cured of their infection—among prior null responders was 40 percent (19 of the 47 prior null responders who remained enrolled in the study). Among the 91 prior partial responders and relapsers, the SVR 24 rate was 68 percent.

Study subjects who saw their HCV viral loads drop by at least 1 log (more than 90 percent) after the four-week peg-IFN/RBV dosing period—roughly 22 percent of prior null responders and 76 percent of prior partial responders/relapsers—were more likely to experience an SVR 24. According to Brownowicki and his colleagues, 55 percent of prior null responders and 70 percent of prior partial responders/relapsers who saw their viral loads decrease by at least 1 log during the first four weeks of treatment were cured of their infection following triple-drug therapy.

Seven percent of the PROVIDE participants discontinued therapy because of side effects. Roughly half of the patients in the study experienced anemia; one-third experienced dysgeusia (distorted sense of taste); and one-quarter experienced a drop in their neutorphil counts.

Victrelis and peg-IFN/RBV, the authors concluded, “achieved high SVR rates regardless of prior response to [peg-IFN/RBV]. The degree of interferon responsiveness after [peg-IFN/RBV] lead-in correlated with prior response and can help predict SVR for prior null responders.”

They add: “The safety profile is comparable to that previously reported for [Victrelis plus peg-IFN/RBV].”