Merck has reported positive results from two pivotal Phase III clinical trials for bezlotoxumab, its investigational antitoxin, to prevent Clostridium difficile (C difficile) infection recurrence.
The trials met their primary efficacy endpoint, which was 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.
This year, the company intends to submit new drug applications (NDAs) seeking regulatory approval in the US, EU, and Canada for bezlotoxumab.
Bezlotoxumab, a selective, fully-human, monoclonal antibody, is designed to neutralise C difficile toxin B, a toxin that can damage the gut wall and cause inflammation, leading to the symptoms of C difficile enteritis, including abdominal pain and watery diarrhea.
There are currently no therapies approved for the prevention of recurrent disease caused by C difficile.
Leeds Teaching Hospitals and University of Leeds and a lead investigator for the studies Dr Mark Wilcox said: "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.
"These results were also demonstrated in patient subgroups known to be at high-risk for C difficile recurrence."
Researchers at the University of Massachusetts Medical School’s MassBiologics Laboratory in conjunction with Medarex have developed bezlotoxumab, which has been licensed to Merck in 2009 to develop as a potential therapeutic for C difficile infection.
The two global, double-blind Phase III trials (MODIFY I and MODIFY II) were conducted to evaluate bezlotoxumab, either alone or in combination with actoxumab, compared to placebo to prevent recurrent C difficile infection in patients on standard of care antibiotics for a primary or recurrent C difficile infection.
Actoxumab is a fully human monoclonal antibody against C difficile toxin A.
The MODIFY I trial enrolled 1,452 patients with median age 65 years in 19 countries and MODIFY II enrolled 1,203 patients with median age 67 years in 17 countries.
The trials were conducted in both hospital and outpatient settings, and the primary endpoint for each study was evaluated through 12 weeks following trial drug administration.