In the United States, C. difficile infects nearly half a million people each year and contributes to around 29,000 deaths. The infection is treated with standard antibiotics, which also wipe out healthy bacteria that normally keep C. difficile under control.
Merck said two Phase 3 studies found 12 weeks of treatment with antibiotics and a one-time infusion of bezlotoxumab, designed to block the ability of a toxin to bind to cells, reduced to about 15% the risk that C. difficile would recur. The studies found that the infection recurred in about 25% of patients treated with antibiotics and a placebo.
“We have therapies to treat the initial episode, but this infection comes back frequently – there is a 25% risk of recurrence after the first time, and that rises to 40% or even 60% after the second infection,” said Nick Kartsonis, associate vice president in clinical research, infectious diseases at Merck.
The studies showed no benefit from a second experimental antibody, actoxumab, either alone or in combination with bezlotoxumab. Merck said the actoxumab arm was stopped for efficacy and safety reasons after an interim analysis.
The studies were presented September 20 at the Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC) and International Congress of Chemotherapy and Infection (ICC) joint meeting in San Diego.
Bezlotoxumab is a selective, fully-human, monoclonal antibody designed to neutralize C. difficile toxin B.
The company said it plans to file before the end of the year for regulatory approval of bezlotoxumab, which it licensed from Massachusetts Biologic Laboratories and Medarex, now owned by Bristol-Myers Squibb.
Side effects, including nausea, diarrhea and urinary tract infection, occurred at similar rates for patients in both the treatment and placebo arms of the trials.
The incidence of C. difficile infection has risen sharply over the last two decades and is now a leading cause of healthcare-acquired infections in community hospitals in the United States, according to the U.S. Centers for Disease Control and Prevention.
Other companies are working on vaccines against C. difficile. Doctors are also treating patients with “stool transplants,” which involves inserting fecal material from a healthy person into the gut of someone with severe diarrhea in order to restore friendly bacteria.