Merck & Co. weeks away from filing first antibacterial mAb
Bezlotoxumab was successful in two Phase III trials against the recurrence of Clostridium difficile (C. difficile) infection when combined with antibiotics.
Merck plans to file new drug applications for the monoclonal antibody in the US, Canada and EU by the end of the year. Currently, there are no therapies approved for the prevention of recurrent disease caused by C. difficile.
Bezlotoxumab’s approval would also make it the first antibody to treat bacterial infection.
Scientists say mAbs would have benefits over small molecule antibiotics because they are less likely to drive antimicrobial resistance and are administered less frequently.
“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 lead investigator Mark Wilcox of the University of Leeds, UK. “These results were also demonstrated in patient subgroups known to be at high risk for C. difficile recurrence.”
C. difficile toxin B can damage the gut wall and cause inflammation, leading to the symptoms of C. difficile enteritis, which include abdominal pain and watery diarrhea. Bezlotoxumab, a fully-human monoclonal antibody, was developed by researchers at the University of Massachusetts Medical School’s MassBiologics Laboratory with Medarex (now part of Bristol-Myers Squibb), and licensed to Merck in 2009.
The studies
Merck’s studies took more than 1,000 patients each and evaluated them over 12 weeks. Participants received either a single infusion of bezlotoxumab, actoxumab (another mAb designed to fight C. difficile),a combination of the two, or a placebo. The actoxumab arm of the study ended early for efficacy and safety reasons.
Both studies had infection recurrence as their primary endpoint – this rate was significantly lower for the bezlotoxumab arms (17.4% and 15.7%) and bezlotoxumab plus actoxumab arms (15.9% and 14.9%), compared to placebos (27.6% and 25.7%). Actoxumab was found not to provide extra benefit on its own or combined with bezlotoxumab, so Merck’s marketing authorisation application is for bezlotoxumab alone.
mAb pipeline
Other companies have mAb antibacterials in Phase I and II. The most mature is AstraZeneca’s compound against S. aureus alpha-toxin in patients with ventilator-associated pneumonia. Aridis Pharmaceuticals is also developing a drug against the same toxin and against P. aeruginosa lipopolysaccharide. Bellus Health, XBiotech and Arsanis also have antibacterials in the works.
