FDA Questions Merck & Co.'s C. Diff Diarrhea Medication’s Efficacy
June 8, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Early regulatory review of Merck & Co. 's bezlotoxumab for diarrhea caused by Clostridium difficile (C. diff), indicates the review panel is questioning whether the drug actually works.
C. difficile, typically referred to as C. diff, is a bacteria that inflames the colon, resulting in severe diarrhea that can be life threatening. It is a common cause of infectious diarrhea in hospitals and nursing homes. According to federal health data, C. diff is the most common microbial cause of health care-related infectious in the U.S.
A U.S. Food and Drug Administration (FDA) briefing document starts with, “We would like the committee to discuss whether the data are adequate to support safety and efficacy of bezlotoxumab for the prevention of Clostridium difficile infection (CDI) recurrence.”
The drug is a fully human monoclonal IgG1/kappa antibody. It binds to one of the C. difficile toxins, which prevents it from binding to cells in the colon. This results in avoiding inflammation of the colon cells.
Trials have shown a decrease in C. difficile recurrent in patients treated with bezlotoxumab, but the FDA expressed concern whether the drug’s efficacy had actually been adequately demonstrated. As summed up by Reuters, “The review said results suggest the drug may ‘negatively affect’ the cure rate of an initial C. difficile episode.”
The drug was developed to neutralize toxin B found in C. difficile. If the drug is approved, it would be prescribed with antibiotics, which are the current standard treatment. There are otherwise no drugs to prevent recurrence on the market.
Bezlotoxumab was developed by Medarex, which was acquired by Bristol-Myers Squibb and then licensed to Merck in 2009.
The FDA briefing states, “While there appears to be a decrease in CDI recurrence with the use of bezlotoxumab, there is concern as to whether the efficacy of bezlotoxumab for the prevention of CDI recurrence has been adequately demonstrated. It was anticipated that the monoclonal antibody would have no impact on clinical cure of the initial CDI episode. However there were numerical differences observed in clinical cure between bezlotoxumab and placebo in both trials. In Study P001, the difference was in favor of placebo whereas the difference was in favor of bezlotoxumab in Study P002.”
According to Merck’s briefing documents, in 2011 there were approximately 29,000 deaths in the U.S. associated with CDI. The Centers for Disease Control and Prevention (CDC) have declared CDI an urgent public health threat.
The Merck files also indicate that the two trials, “demonstrated that the administration of a single IV 10mg/kg dose of bezlotoxumab is superior to placebo in prevention of CDI recurrence (primary endpoint) over a follow-up period of 12 weeks.”
A decision by the FDA is expected by July 23.