A Merck & Co antibody designed to treat a serious hospital-associated infection has cleared two phase III trials, setting up regulatory filings later this year.
The antibody – called bezlotoxumab – targets a toxin produced by the bacterium Clostridium difficile, which generally infects people who are receiving antibiotic treatment and claims thousands of lives every year.
While the bacteria itself usually does not cause any problems, if the natural bacterial balance in the gastrointestinal tract is disturbed it can multiply quickly, with the toxins produced causing symptoms such as diarrhoea and fever.
Outbreaks of the infection generally occur in community hospitals and nursing homes, with half a million cases resulting in around 29,000 deaths in the US in 2011. Around 80% of the fatalities occur in patients aged over 65.
In the two trials, a one-off infusion of bezlotoxumab was shown to reduce the recurrence of C difficile over a 12-week period compared to placebo when used alongside standard antibiotic therapy for the infection. The recurrence rate with antibody treatment was around 15%-17%, while in the placebo group it was in the 26%-28% range.
Another antibody being developed as a combination with bezlotoxumab, actoxumab, was dropped from the study for “efficacy and safety reasons” after an interim analysis, according to Merck. The company plans to file for approval of beclotoxumab in the US, Europe and Canada before the end of the year.
“Recurrence is a major challenge with C. difficile infection, and novel approaches are needed to help prevent the cycle of C. difficile recurrence,” said Dale Gerding of Loyola University Chicago Stritch School of Medicine, who was a lead investigator for the studies.
The results were presented over the weekend at the Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC) and International Congress of Chemotherapy and Infection (ICC) joint meeting in San Diego.
Bezlotoxumab and actoxumab were developed in house by Merck in partnership with a subsidiary of Bristol-Myers Squibb (BMS). Merck bolstered its anti-infectives pipeline last year with the $8.4bn acquisition of Cubist Pharmaceuticals, which added a range of antibiotics including recently-approved Sivextro (tedizolid phosphate) and Zerbaxa (ceftolozane/tazobactam).
Merck also has relebactam (MK-7655) in mid-stage trials as an intravenous treatment for acute bacterial infections.