The effectiveness of REBYOTA was evaluated using a Bayesian analysis of data from a randomized, double-blind, placebo-controlled, multicenter Phase 3 study (Study 1), which formally integrated treatment success rates from a placebo-controlled Phase 2 study (Study 2). Enrolled adults in both studies were 18 years of age or older and had a confirmed diagnosis of recurrent CDI (one or more episodes in Study 1; two or more episodes in Study 2) which was defined as diarrhea (passage of 3 or more loose bowel movements within a 24-hour period for 2 consecutive days) and a positive stool test for C. difficile toxin or toxigenic C. difficile, or had at least two episodes of severe CDI resulting in hospitalization within the last year. Enrolled adults were required to have completed at least 10 consecutive days of antibiotic therapy and have their CDI under control (<3 unformed/loose, i.e., Bristol Stool Scale type 6-7, stools/day for 2 consecutive days). A minimum of 24 hours to a maximum of 72 hours (Study 1) or 24 hours to a maximum of 48 hours (Study 2) antibiotic washout period was required prior to administration of the assigned study treatment. In Study 1, enrolled adults were randomized 2:1 to a single dose of REBYOTA or placebo respectively. In Study 2, randomization was 1:1:1 to receive two doses of REBYOTA, two doses of placebo, or one dose of REBYOTA and one dose of placebo, administered 7±2 days apart. Only data from the REBYOTA one-dose group and the placebo group are described below and were integrated in the Bayesian analysis.

In the integrated efficacy analysis set, the demographic profile and baseline recurrent CDI characteristics of treated adults were similar in the REBYOTA and placebo groups. In Study 1, a total of 262 adults were randomized and treated, of which 177 adults received REBYOTA and 85 received placebo. Adults had a mean age of 60.1 years with 45.4% of adults 65 years of age or older, were mainly white (92.0%) and female (69.1%). In this study, 32.8% of adults received REBYOTA or placebo for their first recurrence of CDI. In Study 1, 87.4% of adults had received vancomycin alone prior to treatment. In Study 2, 39 adults received one dose of REBYOTA and one dose of placebo and 43 adults received two doses of placebo. Adults in these two groups had a mean age of 59.8 years with 42.7% of adults 65 years of age or older, were mainly white (97.6%) and female (63.4%). In this study, 89.0% of adults had received vancomycin prior to treatment.

Treatment success was defined as the absence of CDI diarrhea within 8 weeks of blinded treatment. CDI diarrhea was defined as the passage of ≥ 3 unformed/loose stools in ≤ 24 hours for at least 2 consecutive days and a positive stool test for the presence of C difficile toxin at the time of the diarrhea.

In the Bayesian analysis, the estimated rate of treatment success was significantly higher in the REBYOTA group (70.6%) than in the Placebo group (57.5%) through 8 weeks after completing blinded treatment, resulting in a difference of 13.1 percentage points (95% Credible Interval: 2.3, 24.0) which corresponds to a 99.1% posterior probability that REBYOTA is superior to Placebo (Table 2).

Study 1 evaluated sustained clinical response which was defined as treatment success at 8 weeks and no CDI event through 6 months after the last dose during the blinded period. The difference in sustained clinical response rate (9.1%; 95% CI: -3.6%, 21.7%) was not statistically significant between the REBYOTA (65.5%) and the placebo groups (56.5%).