Colon to Rectum
N Engl J Med. 2022;386(3):220–9
SER-109, an oral microbiome therapy for recurrent Clostridioides difficile infection
Background: Current therapies for recurrent Clostridioides difficile infection (CDI) do not address the disrupted microbiome, which supports C. difficile spore germination into toxin-producing bacteria. SER-109 is an investigational microbiome therapeutic composed of purified Firmicutes spores for the treatment of recurrent CDI.
Methods: The authors conducted a phase 3, double-blind, randomized, placebo-controlled trial in which patients who had had ≥ 3 episodes of CDI (inclusive of the qualifying acute episode) received SER-109 or placebo (4 capsules/day for 3 days) 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 CDI recurrence up to 8 weeks after treatment. Diagnosis by toxin testing was performed at trial entry, and randomization was stratified according to age and antibiotic agent received. Analyses of safety, microbiome engraftment, and metabolites were also performed.
Results: Among the 281 patients screened, 182 were enrolled. The percentage of patients with recurrence of CDI was 12% in the SER-109 group and 40% in the placebo group (relative risk [RR] = 0.32; 95% confidence interval [CI]: 0.18–0.58; p < 0.001 for a RR of < 1.0; p < 0.001 for a RR of < 0.833). SER-109 led to less frequent recurrence than placebo in analyses stratified according to age stratum (RR = 0.24 [95% CI: 0.07–0.78] for patients < 65 years of age and 0.36 [95% CI: 0.18–0.72] for those ≥ 65 years) and antibiotic received (RR = 0.41 [95% CI: 0.22–0.79] with vancomycin and 0.09 [95% CI: 0.01–0.63] with fidaxomicin). Most adverse events were mild to moderate and were gastrointestinal in nature, with similar numbers in the 2 groups. SER-109 dose species were detected as early as week 1 and were associated with bile-acid profiles that are known to inhibit C. difficile spore germination.
Conclusions: In patients with symptom resolution of Clostridioides difficile infection after treatment with standard-of-care antibiotics, oral administration of SER-109 was superior to placebo in reducing the risk of recurrent infection. The observed safety profile of SER-109 was similar to that of placebo.