Efficacy and Safety of Fecal Microbiota, Live-jslm in Older Participants With Recurrent Clostridioides difficile Infection and Underlying Comorbidities: An Ad Hoc Analysis of an Open-Label, Phase 3 Study

Introduction: Advanced age and certain underlying comorbidities are among the risk factors for recurrent Clostridioides difficile infection (rCDI). PUNCH CD3-OLS (NCT03931941) is an ongoing, open-label, phase 3 trial designed to evaluate the efficacy and safety of fecal microbiota, live-jslm (RBL; REBYOTA™, previously known as RBX2660), the first microbiota-based live biotherapeutic product approved by the FDA to prevent rCDI in adults. Here, we report an ad hoc subgroup analysis of older participants with common comorbidities. Methods: PUNCH CD3-OLS participants are ≥18 years old with documented rCDI as determined by the treating physician and confirmed using standard-of-care (SOC) methods, including NAAT or EIA assays. Within 24 h to 72 h after completing SOC antibiotics, participants received a single dose of RBL administered rectally. In this subgroup analysis, outcomes of participants ≥65 years old with at least one of the following underlying comorbidities were assessed: cardiac disorders, chronic kidney disease (CKD), and gastrointestinal (GI) disorders. The primary outcome was treatment success, defined as absence of CDI recurrence for 8 weeks after treatment. Participants were monitored for recurrence and treatment-emergent adverse events (TEAEs) up to 6 months after treatment. Results: In the modified intent-to-treat population, 43% (172/402) of participants with adjudicated outcomes were ≥65 years old. Of these 172 participants, 50% had cardiac disorders (including atrial fibrillation and coronary artery disease), 16% had CKD, and 53% had GI disorders (including gastroesophageal reflux disease, irritable bowel syndrome, and ulcerative colitis); 27% of participants were in 2 of the comorbidity subgroups and 8% were in all 3. Across all subgroups, participants had an average of ≥3 prior CDI episodes and Charlson Comorbidity Index scores ≥5 at the time of enrollment. RBL treatment success rates were 63% for those with cardiac disorders, 63% for those with CKD, and 70% for those with GI disorders. In the safety population (N = 483), the overall incidence of TEAEs in older participants with cardiac disorders, CKD, or GI disorders was 73%, 70%, and 65%, respectively; most TEAEs were mild or moderate in severity and deemed unrelated to treatment by the treating physician. Conclusion: RBL treatment remains effective in a cohort of older participants with multiply recurrent CDI and common comorbidities. The safety profile was consistent with that observed in previous clinical trials investigating RBL.