Boceprevir for HCV Wins Unanimous FDA Committee Recommendation

SUMMARY
FDA Antiviral Drugs Advisory Committee voted 18-0 to recommend approval of protease inhibitor boceprevir (Victrelis) for people with hard-to-treat HCV genotype 1.

By Liz Highleyman

The advent of direct-acting antiviral agents that target different steps of the hepatitis C virus (HCV) lifecycle is expected to revolutionize hepatitis C treatment. These drugs will initially be used in combination with pegylated interferon and ribavirin -- increasing the cure rate and potentially allowing shorter therapy -- but combinations of all oral drugs are currently under study.

The first drugs out of the pipeline are 2 HCV protease inhibitors, Merck's boceprevir and Vertex's telaprevir. On Wednesday (April 27), the Antiviral Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) gave a unanimous recommendation for approval of boceprevir.

The committee hearing for telaprevir was underway on Thursday, as HIVandHepatitis.com was preparing for publication, and it too will likely be recommended for approval.

On Wednesday the committee reviewed clinical trial data showing that boceprevir added to pegylated interferon plus ribavirin cured more patients -- and in less time -- than standard therapy alone. The improvement in response rates was particularly notable for people with HCV genotype 1 and those who did not respond or relapsed with a prior course of standard treatment.

Sustained virological response rates for genotype 1 prior non-responders were around 60% with boceprevir plus pegylated interferon/ribavirin, compared with about 20% for standard therapy alone. For treatment-naive patients, cure rates approached 70% with boceprevir compared with about 40% for standard treatment.

Boceprevir is generally well-tolerated, but it increases the risk of developing anemia (already a concern with ribavirin). Studies also showed an increase in reports of suicidal or homicidal ideation, but the committee said it was "difficult to make any meaningful clinical conclusions" based on this.

While the committee voted 18 to 0 in favor of approval, it did recommend further studies looking at how to improve response in difficult-to-treat groups such as people of African descent and patients with liver cirrhosis. It also remains unclear how well "null responders" who do not experience substantial HCV viral load reduction during the early weeks of therapy will fare, and how best to use response-guided therapy.

"The positive recommendation brings us one step closer to bringing Victrelis to men and women who need it, and reinforces our ongoing commitment to developing innovative therapies to treat chronic hepatitis C," said Merck Research Laboratories president Peter Kim, PhD, in a company press release. "We're pleased with the panel's decision and look forward to working with the FDA as it continues to evaluate the application for Victrelis."

The full FDA is not required to accept committee recommendations, but it typically does so. Agency approval of boceprevir is expected by the end of May, and the drug should be commercially available by the end of the summer.

Briefing materials on boceprevir provided by the FDA and Merck are available online at: