Rebyota Demonstrates Safety and Efficacy Against rCDI, Including in High-Risk Patients

Rebyota (fecal microbiota, live jslm) was the first microbiota-based live biotherapeutic product to be approved by the US Food and Drug Administration (FDA). The rectally administered treatment, developed by Ferring Pharmaceuticals, is indicated to prevent recurrent Clostridioides difficile infection (rCDI) in adults who previously received antibiotic treatment for rCDI.

A post hoc analysis, presented last week at the 2023 MAD-ID Annual Antimicrobial Stewardship Meeting, analyzed patient outcomes and treatment-related variables among participants with documented rCDI.

The phase 2 and phase 3 randomized, double-blind, placebo-controlled trials grouped patients by rCDI risk factors. The participants received either Rebyota or placebo after completing initial CDI antibiotic therapy.

The investigators defined treatment success as the absence of CDI diarrhea within 8 weeks of receiving the study drug. After pooling data from the 2 trials, Bayesian model-estimated treatment success rates and their 95% credible intervals were calculated for the matched modified intent-to-treat populations.

Patient rCDI risk factors included age of 65 years and older, prior CDI, proton pump inhibitor/H2 receptor antagonist use, baseline chronic kidney disease, tape 2 diabetes mellitus, and congestive heart failure. Treatment-related variables included CDI diagnostic test, oral vancomycin duration, and CDI antibiotic washout duration. Treatment-emergent adverse events for the double-blind study period were summarized within 8 weeks.

The total study population comprised 216 participants treated with a single dose of Rebyota and 128 placebo-treated patients. Differences between the 2 study groups were similar to the total population for most risk factors, including total risk factors (13.1%), age of 65 years and older (12.2%), more than 3 prior CDI episodes (20.8%), use of proton pump inhibitor or H2 receptor antagonist, type 2 diabetes mellitus (10.9%), and chronic kidney disease (13.3%).

Treatment effect sizes were similar between CDI tests, higher for oral vancomycin courses, and higher for antibiotic washout periods of 3 days. The largest reductions in the rate of rCDI in Rebyota versus placebo recipients were observed in patients with 3-day washout (24%) and more than 3 prior CDI episodes (20.8%). Most participants with chronic kidney disease, type 2 diabetes mellitus, or chronic heart failure experienced treatment-emergent adverse events that were mild-to-moderate in severity and related to preexisting conditions.

The investigators concluded that these findings evidence the safety and efficacy of Rebyota across patient subgroups, including in patients at a high risk of rCDI.

This study, “Fecal Microbiota, Live-jslm for the Prevention of Recurrent Clostridioides difficile Infection (CDI): Subgroup Analysis of PUNCH CD2 and PUNCH CD3 Participantswith Risk Factors for CDI Recurrence,” was presented by author Andrew Skinner, MD, as an abstract at the 2023 MAD-ID Annual Antimicrobial Stewardship Meeting.