Merck & Co. said the FDA has delayed to October a decision on its application to market bezlotoxumab for the prevention of Clostridium difficile infection recurrence, after requesting more clinical data from the company.
In a statement late yesterday, Merck said the FDA requested unspecified “new data and analyses” from the MODIFY I and MODIFY II clinical trials, whose data support the company’s Biologics Licensing Application for bezlotoxumab.
As a result, the agency extended its “goal” date under the Prescription Drug User Fee Act (PDUFA) for a decision on the application by 3 months, from tomorrow to October 23.
“Merck looks forward to continuing to work with the FDA on the review of the bezlotoxumab BLA,” the company stated after the close of trading.
Merck also cited a 10-to-5 vote, with one abstention, recommending FDA approval by the agency’s Antimicrobial Drugs Advisory Committee on June 9.
While the advisory committee concluded that bezlotoxumab showed substantial evidence of efficacy and safety in preventing the recurrence of C. difficile infection, some panel members took issue with the size of the population randomized to the bezlotoxumab-plus-antibiotic treatment arms in MODIFY I and MODIFY II—a combined 800 patients—saying larger studies would have better pinpointed which patients would likely benefit most from the drug.
MODIFY is short for Monoclonal Antibodies for C. Difficile Therapy. In MODIFY I, patients receiving standard-of-care antibiotics for C. difficile were randomized to receive a single, one-time infusion of either bezlotoxumab , actoxumab, the combination of bezlotoxumab and actoxumab, or placebo. The actoxumab arm was stopped for efficacy and safety reasons after an interim analysis.
In the MODIFY II study, patients receiving standard-of-care antibiotics for C. difficile were randomized to receive a single, one-time infusion of either bezlotoxumab, bezlotoxumab and actoxumab, or placebo.
Bezlotoxumab is a selective, fully human, monoclonal immunoglobulin G1 (IgG1)/kappa antibody designed to neutralize C. difficile toxin B, which can damage the gut wall and cause inflammation, leading to the symptoms of C. difficile enteritis.
Last September, Merck trumpeted Phase III results from MODIFY I and MODIFY II, which showed bezlotoxumab meeting its primary efficacy endpoint of reducing C. difficile recurrence through week 12 compared to placebo, when used with standard-of-care antibiotics for the treatment of C. difficile.
Merck licensed rights to bezlotoxumab in 2009 from Medarex, which was acquired later that year by Bristol-Myers Squibb, and the University of Massachusetts Medical School, where researchers at the MassBiologics Laboratory developed the drug.