Study data published in the New England Journal of Medicine support the efficacy of a novel microbiome therapeutic comprised of purified Firmicutes spores for the treatment of recurrent Clostridioides difficile (C difficile) infection.
This phase 3 randomized clinical trial was conducted at 56 clinical sites in Canada and the United States between July 2017 and September 2020. Eligible patients were aged at least 18 years and had experienced 3 or more C difficile episodes within 12 months, inclusive of the episode treated during the study period. Patients underwent standard-of-care antibiotic treatment with vancomycin or fidaxomicin prior to randomization.
After stratification by age and antibiotic treatment, patients were randomly assigned in a 1:1 ratio to receive SER-109 or placebo administered as 4 oral capsules once daily over 3 consecutive days.
The primary outcome was C difficile recurrence at 8 weeks. Secondary outcomes included changes in species composition and bile-acid concentrations in the SER-109 vs placebo groups. Engraftment of SER-109 dose species was also assessed. Adverse events were monitored throughout the trial duration.
A total of 182 patients were enrolled and randomly assigned: 89 patients to the SER-109 arm and 93 to the placebo arm. Demographic and clinical characteristics were comparable between groups. Mean age in the total cohort was 65.5 years; 66% were women and 93% were White. Overall, 149 patients (82%) completed 8 weeks of follow-up.
The proportion of patients with recurrence was significantly lower in the SER-109 group compared with the placebo group (12% vs 40%), with a relative risk [RR] of 0.32 (95% CI, 0.18-0.58; P <.001). This association persisted in analyses stratified by age and antibiotic treatment course: RRs were 0.24 (95% CI, 0.07-0.78) among patients aged <65 years, 0.36 (95% CI, 0.18-0.72) among patients aged ≥65 years, 0.41 (95% CI, 0.22-0.79) among patients who took vancomycin, and 0.09 (95% CI, 0.01-0.63) among those who took fidaxomicin.
The most common adverse events were gastrointestinal conditions, the majority of which were mild to moderate in nature. Three deaths occurred in the SER-109 arm but were considered unrelated to the study drug.
Engraftment of SER-109 dose species was seen by week 1 and maintained through week 8 in the SER-109 group. Greater increases in secondary bile acids from baseline were observed in the SER-109 arm compared with the placebo arm. Patients who received SER-109 displayed bile acid profiles marked by declines in proinflammatory Enterobacteriaceae bacteria and increases in Firmicutes bacteria.
As far as study limitations, investigators cited the small number of patients enrolled from minority populations; further study is necessary to determine the efficacy of SER-109 in Black and Hispanic individuals.
Results from this trial demonstrate the superiority of novel drug SER-109 vs placebo in reducing the risk for C difficile recurrence after standard-of-care antibiotics treatment. The observed safety profile of SER-109 was comparable to that of placebo, with no study drug-related serious adverse events observed. SER-109 was also associated with bile acid profiles known to inhibit C difficile spore germination. “We continue to collect data [on SER-109] from our open-label study, SERES-013,” investigators wrote. “Insights into the pharmacologic properties of this oral microbiome therapeutic have implications not only for treatment of recurrent C. difficile infection but also for other diseases with pathogenesis that may be rooted in microbiome disruption.”
Disclosure: This research was supported by Seres Therapeutics. Please see the original reference for a full list of disclosures
Feuerstadt P, Louie TJ, Lashner B, et al. SER-109, an oral microbiome therapy for recurrent Clostridioides difficile infection. N Engl J Med. 2022;386(3):220-229. doi: 10.1056/NEJMoa2106516