FDA Panel Urges Approval of Hepatitis C Drug

April 27, 2011 -- In an18-0 vote, an FDA advisory panel recommended approval of the drug boceprevir to treat hepatitis C.

Panel members called boceprevir, manufactured by Merck & Co., a weapon in the fight against chronic hepatitis C virus (HCV) genotype 1 infection.  

Boceprevir is a protease inhibitor that has proven effective in adults with liver disease who have been untreated or who have failed previous therapy. Chronic HCV genotype 1 infection is the most common form of hepatitis in the U.S. and also the most difficult to treat.

Despite the committee’s affirmative vote, the advisors also had reservations about  boceprevir’s widespread usage.   

The drug has proven to reduce the viral load to levels that are undetectable in more than a third of the HCV patients who use it. But the main contention concerned increased incidents and severity of anemia when the drug is used in addition with a pair of commonly used HCV drugs, pegylated interferon and ribavirin.

Additionally, there was an increase in patients’ reported psychiatric symptoms and suicidal thoughts among participants in the drug’s trials.

The problem, according to panel members, is that the studies show great promise, but the small sample size of 1,500 patients among two trials and the lack of diversity among the trial’s participants raise questions. The committee raised nearly 40 points they wished to have Merck’s researchers investigate.

While praising the drug as the greatest advancement to date in any HCV regimen, Marc Ghany, MD, of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, summarized the feelings of his fellow advisory board members:  "The data speak for themselves. The challenge is going be how to use this medication in the greater population." 

Questions for Drugmaker

Boceprevir isn’t effective in every patient, and the advisory committee criticized Merck researchers for not having the answers to questions they felt should have been considered in advance of coming before them.  Patient representative Lynda Marie Dee, JD, of Baltimore, pulled no punches in her displeasure. “There are no drug interaction studies. I’m shocked we don’t have studies on depression.  It’s very disappointing that this hasn’t already been done.” 

A number of the panelists questioned Merck about not having more African-Americans in their studies on the drug. While the company included a separate analysis of results in African-American patients who did take part in this particular trial, medical history shows that this is a population that typically does not respond well to standard therapy. 

Other suggestions included further studies to determine boceprevir’s effectiveness in patients with co-existing conditions including diabetes, cirrhosis, depression, and anemia.  Committee members also wanted to know about interactions between the HCV drug and oral contraceptives, alcohol, and over-the- counter medications.  All questions Merck explained would require more research. 

The acting chair of the advisory committee, Victoria Cargill, MD, director of the Minority Research Office of AIDS Research at the National Institutes of Health, says although questions do remain, “This changes the game.  And I hope for the continued advancement in treating these patients.” 

The FDA is not required to accept the recommendation of its advisory panel, but it often does. The final word from the FDA should be handed down by the middle of May.