Merck & Co’s experimental drug to treat the most common hospital-associated infectious diarrhea
* Clostridium difficile * warrants approval, an advisory panel to the U.S. Food and Drug Administration said on Thursday.
The panel voted 10-5, with one abstention, that the drug, bezlotoxumab, was effective in preventing a recurrence of infection with Clostridium difficile, or C. difficile, a germ that causes inflammation of the colon and potentially fatal diarrhea.
The FDA is not obliged to follow the advice of its advisory panels but typically does.
The panel’s vote follows an internal review by FDA staff which found an apparent decrease in recurrence of C. difficile but expressed concern as to whether the drug could hurt the cure rate of the initial C. difficile episode.
Panelists who voted in favor of the drug acknowledged the FDA’s concerns but said they were persuaded there was a need for new targeted therapies and this one seems effective.
“We haven’t had a new drug for C. difficile in our armamentarium for some time,” Dr. Joanna Schaenman, assistant professor of medicine at UCLA David Geffen School of Medicine, said.
MORE about bezlotoxumab : https://cdifffoundation.org/category/clinical-trials/
Merck & Co. bezlotoxumab was successful in two Phase III trials against the recurrence of
Clostridium difficile (C. difficile) infection when combined with antibiotics.
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.
The FDA is due to make its decision by July 23.
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