Oral microbiome therapeutic shows potential in reducing recurrent C. difficile infection
An investigational oral microbiome therapeutic was superior to placebo in reducing the risk for recurrent Clostridioides difficile infection among patients with three or more episodes, according to the results of a phase 3 trial.
The double-blind, randomized, placebo-controlled ECOSPOR III study evaluated SER-109, which is composed of live purified Firmicutes bacterial spores. Seres Therapeutics said it expects to finalize a Biologics License Application submission for SER-109 with the FDA by mid-2022.
“Clostridioides difficile infection has been estimated to be associated with more than 460,000 cases of illness and 20,000 deaths annually in the United States,” Paul Feuerstadt, MD, assistant clinical professor of medicine at the Yale University School of Medicine, and colleagues wrote in The New England Journal of Medicine.
“Clinical outcomes remain suboptimal because current therapies do not address fundamental aspects of the two-phase life cycle of this pathogen or disease pathogenesis,” they wrote. “Vancomycin and fidaxomicin lead to symptom relief by killing toxin-producing C. difficile bacteria that cause colonic inflammation and debilitating diarrhea. However, antibiotic agents do not kill C. difficile spores, which can rapidly germinate into toxin-producing vegetative bacteria after treatment discontinuation.”
For the study, Feuerstadt and colleagues enrolled adult patients with three or more episodes of C. difficile infection in 12 months and randomly assigned them in a 1:1 ratio to receive SER-109 or placebo after standard-of-care antibiotic treatment.
“The primary efficacy objective was to show superiority of SER-109 as compared with placebo in reducing the risk of C. difficile infection recurrence up to 8 weeks after treatment,” they explained.
Among the 182 participants, 12% in the treatment arm and 40% in the placebo arm had recurrent C. difficile (RR = 0.32; 95 CI, 0.18-0.58). The study demonstrated that SER-109 led to less frequent C. difficile recurrence than placebo in an analysis stratified according to age (RR = 0.24; 95% CI, 0.07-0.78 for patients aged younger than 65 years and RR = 0.36; 95% CI, 0.18-0.72 for those aged 65 years and older) and by antibiotic received (RR = 0.41; 95% CI, 0.22-0.79 with vancomycin and RR = 0.09; 95% CI, 0.01-0.63 with fidaxomicin).
Most of the adverse events reported by patients were mild to moderate and were gastrointestinal in nature, with similar numbers in the two groups, the researchers said.
“Clinical outcomes in recurrent C. difficile infection may be improved by using a two-pronged treatment approach: antibiotics to kill toxin-producing bacteria followed by a microbiome therapeutic to inhibit C. difficile spore germination and bacterial replication through microbiome repair,” the authors wrote. “In this trial, SER-109 was superior to placebo in reducing the risk of C. difficile infection recurrence.”
New England Journal of Medicine publishes data from the ECOSPOR III phase 3 study evaluating investigational microbiome therapeutic SER-109 in recurrent C. difficile infection. https://ir.serestherapeutics.com/news-releases/news-release-details/new-england-journal-medicine-publishes-data-ecospor-lll-phase-3. Published Jan. 19, 2022. Accessed Jan. 20, 2022.