Two Phase 3 clinical studies have shown that Merck's investigational antibody bezlotoxumab reduces the recurrence of Clostridium difficile (C. difficile) infections when used alongside standard antibiotic treatments.
With its Phase 3 studies meeting primary efficacy endpoints set, Merck is gearing up to submit new applications for the drug to gain regulatory approval for bezlotoxumab in the European Union, the United States and Canada this year. The results of the studies have particular significance because there are currently no treatment options approved to prevent C. difficile recurrence.
Presented at the joint meeting of the International Congress of Chemotherapy and Infection and the Interscience Conference of Antimicrobial Agents and Chemotherapy, the results of the studies showed that a single, one-time infusion of bezlotoxumab, given in conjunction with standard antibiotic treatment for the infection, dramatically reduced the recurrence of C. difficile compared to just antibiotic treatment alone over the course of a 12-week period.
Not an antibiotic, bezlotoxumab is a selective, fully-human, monoclonal antibody made to neutralize toxin B of C. difficile, which can cause inflammation and damage intestinal walls and lead to symptoms like watery diarrhea and abdominal pain. It was licensed to Merck in 2009 and further developed as a potential treatment for C. difficile infections.
Conducted in both outpatient and hospital settings, the Phase 3 studies involved 1,452 patients in 19 countries and 1,203 patients in 17 countries, respectively. In the MODIFY I study, subjects were randomized to receive a one-time dose of either actoxumab or bezlotoxumab, the combination of the two or a placebo. In the MODIFY II study, participants were randomized to receive a one-time dose of bezlotoxumab, the combination of actoxumab and bezlotoxumab or placebo.
In both studies, results showed that the rate of recurrence in C. difficile infections was significantly lower where bezlotoxumab was administered, whether on its own or in combination with actoxumab, compared to placebo. Adverse reactions were also similar in the bezlotoxumab and placebo groups. Actoxumab did not improve efficacy when combined with bezlotoxumab so the latter was singled out as possible treatment for C. difficile recurrence.
C. difficile infection has substantially risen over the last 20 years, with the U.S. Centers for Disease Control and Prevention estimating that the condition caused nearly half a million infections in the country in 2011. Out of that number, 29,000 deaths were reported, most of which occurring within the first month of initially being diagnosed. Eight out of 10 C. difficile-related deaths occurred in patients at least 65 years of age.
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