One win, one loss in Merck's PhIII double header for C. diff

Dr. Dale Gerding

Merck ($MRK) says that it's ready to apply for EU and U.S. marketing approval for the anti-infective bezlotoxumab, flagging a pivotal clinical success which arrived four years after the pharma giant launched its late-stage program. But the pharma giant also sounded taps for a related Phase III effort on actoxumab.

In-licensed from Medarex and the University of Massachusetts Medical School back in 2009, bezlotoxumab plus standard of care beat out a standard-care arm in the reduction of C. difficile recurrence in high-risk patients through week 12, according to investigators. Merck released the top-line results at the ICAAC conference in San Diego over the weekend.

The Phase III win highlights Merck's renewed commitment to developing anti-infectives for its acute care portfolio, underscored in its recent $9.5 billion buyout of Cubist. Bezlotoxumab, though, is not an antibiotic. Rather it's an antibody designed to disarm C. diff, preventing infections that kill tens of thousands of people each year.

Bezlotoxumab was studied alone and in combination with actoxumab as MK-3415A, but Merck says that its other antibody failed to produce the kind of efficacy needed to push ahead on an approval. More than 2,600 patients were recruited for two Phase III studies, but only bezlotoxumab will be filed.

The acquisition marked an ongoing surge of interest in developing new antibiotics and anti-infectives, which have been earning fresh incentives as health system officials cry out for new weapons to use against drug-resistant pathogens. Roche has also been stepping up, intrigued by the high-margin market for antibiotics that can be developed for the hospital market.

"Recurrence is a major challenge with C. difficile infection, and novel approaches are needed to help prevent the cycle of C. difficile recurrence," said Dr. Dale Gerding, a professor of medicine at Loyola University Chicago Stritch School of Medicine in Maywood, IL, and a lead investigator for the studies.

Among the biotechs focused on new therapies to prevent the recurrence of C. diff infections is Seres Therapeutics, which has a lead program focused on the same population of patients as Merck.

A success for Phase III is cause for cheer at Merck, which has been engaged in an R&D turnaround over the past couple of years. It's franchise win came with a pioneering approval in cancer, for Keytruda, with a key Phase III effort on hepatitis C that promises to eventually provide some more competition to Gilead's ($GILD) groundbreaking effort in that field. Merck is still engaged in a long-term restructuring that has claimed thousands of jobs.

- here's the release