San Diego, California – Merck & Co. Inc., announced results from two Phase III trials of its developed antibody called Bezlotoxumab, for the prevention of recurrent Clostridium difficile. Results were presented at the International Conference on Antimicrobials and Chemotherapy and the International Congress of Chemotherapy (ICAAC/ICC) 2015 annual gathering on Sunday.

“The incidence and severity of C. difficile infection have risen significantly over the last decade, leading to an increase in hospitalizations, health care costs and mortality.  Although there are approved antibiotics for this infection, recurrence after treatment occurs in 15% to 35% of adult patients, and there are no therapies approved for the prevention of recurrent disease,” explained the report.

Merk-Co-Clostridium
Credit: Sky News

The pharmaceutical company stated that two Phase III studies found that after a 12 weeks treatment with antibiotics and a single infusion of bezlotoxumab, the risks of having any recurrence of C. difficile, which can cause a deadly diarrhea, were reduced by 15%. Other results showed that the infection reappeared in 25% of patients treated with antibiotics and a placebo.

According to Dr. Mark Wilcox, from Leeds Teaching Hospitals and University of Leeds, UK, and a lead investigator of the study, “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. These results were also demonstrated in patient subgroups known to be at high risk for C. difficile recurrence.”

Furthermore, the analysis also examined a second experimental antibody called actoxumab. It was used both alone or in combination with bezlotoxumab. However, results didn’t show any actual benefit for its us and Merck said the actoxumab was stopped for efficacy and safety reasons after an interim analysis.

The company plans to file for regulatory approval of bezlotoxumab before the end of this year. However, side effects, including nausea, diarrhea and urinary tract infection, occurred at similar rates for patients in both the treatment and placebo sides of the trials.

Bezlotoxumab

Bezlotoxumab was developed by scientists at the University of Massachusetts Medical School’s MassBiologics Laboratory in association with Medarex, which is now part of Bristol-Myers Squibb. It was licensed to Merck in 2009 for its development as a potential treatment for C. difficile infection.

Bezlotoxumab is not an antibiotic, it is a selective monoclonal antibody created to neutralize C. difficile toxin B, which can injure the gut wall and cause inflammation, leading to common symptoms of C. difficile enteritis. Symptoms may include abdominal pain and severe diarrhea.

“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, professor of medicine, Loyola University Chicago Stritch School of Medicine, Maywood, Ill., and a lead investigator for the studies.

The Infection

In the US, C. difficile, which is commonly treated with standard antibiotics, infects almost 500,000 people annually, and contributes to nearly 29,000 deaths every year.

According to the US Centers for Disease Control and Prevention the occurrence of C. difficile infection has risen significantly over the last two decades and is now a leading cause of healthcare-acquired infections in hospitals and health centers in the US. The risk of having the infection is higher in certain populations, including people of age 65 and older, or those with a compromised immune system.

Moreover, other companies are working on vaccines against C. difficile. Doctors are also treating patients with “stool transplants,” which is a procedure that involves inserting fecal material from a healthy person into the gut of someone with severe diarrhea in order to restore friendly bacteria.

Source: ASM Society