Bezlotoxumab reduces C. difficile infection recurrence in Phase 3 trials

Two Phase 3 clinical studies of Merck’s bezlotoxumab, an investigational antitoxin for prevention of Clostridium difficile (C. difficile) infection recurrence, met their primary efficacy endpoint: the reduction in C. difficile recurrence through week 12 compared to placebo, when used in conjunction with standard of care antibiotics for the treatment of C. difficile.

Based on these results, the company plans to submit new drug applications seeking regulatory approval of bezlotoxumab in the US, EU and Canada in 2015. Currently, there are no therapies approved for the prevention of recurrent disease caused by C. difficile.

“Results of these studies showed that a single, one-time infusion of the antitoxin bezlotoxumab given with standard of care C. difficile antibiotic treatment significantly reduced the recurrence of C. difficile infection compared to standard of care alone, and demonstrated this benefit over a 12-week period,” said Dr Mark Wilcox, Leeds Teaching Hospitals and University of Leeds, U.K., and a lead investigator for the studies. “These results were also demonstrated in patient subgroups known to be at high risk for C. difficile recurrence.”

Bezlotoxumab is a selective, fully-human, monoclonal antibody

Bezlotoxumab is not an antibiotic. It is a selective, fully-human, monoclonal antibody designed to neutralize C. difficile toxin B, a toxin that can damage the gut wall and cause inflammation, leading to the symptoms of C. difficile enteritis, which include abdominal pain and watery diarrhoea. Bezlotoxumab was developed by researchers at the University of Massachusetts Medical School’s Mass Biologics Laboratory in conjunction with Medarex (now part of Bristol-Myers Squibb), and licensed to Merck in 2009 for development as a potential therapeutic for C. difficile infection.

Two global, Phase 3, double-blind studies were conducted to evaluate bezlotoxumab, either alone or in combination with actoxumab (a fully human monoclonal antibody against C. difficile toxin A), compared to placebo for the prevention of recurrent C. difficile infection in patients on standard of care antibiotics for a primary or recurrent C. difficile infection. The MODIFY I study 1452 patients in 19 countries and the MODIFY II study enrolled 1203 patients in 17 countries.

In both MODIFY I and MODIFY II, the rate of C. difficile infection recurrence through week 12, the primary efficacy endpoint, was significantly lower in the bezlotoxumab arms and the combination bezlotoxumab and actoxumab arms compared to the placebo arms.