Chopra, Teena

Abstract Background Fecal microbiota, live-jslm (RBL) is FDA-approved for prevention of recurrent Clostridioides difficile infection (rCDI) in adults following completion of antibiotic treatment. The safety and efficacy of RBL have been demonstrated in trials, but few studies have evaluated outcomes in real-world populations. The primary objective of ROAR (NCT05835219) is to assess RBL effectiveness in reducing rCDI through 8 weeks in clinical practice. Table 1. Treatment success rates by subgroup Methods ROAR is an ongoing, prospective, multicenter, open-label, non-interventional registry of patients receiving RBL for rCDI prevention in the United States. Adults who completed antibiotics for rCDI and are not in an interventional trial are eligible. The primary endpoint assesses the proportion of patients who experience treatment success (no CDI recurrence through 8 weeks). Other objectives describe rCDI management in real-world clinical practice and adverse events (AEs) after RBL administration. This analysis includes patients who received RBL within 30 days of completing antibiotics for rCDI. Results As of September 18, 2024, 76 patients received RBL within 30 days of completing antibiotics and completed 8 weeks of follow-up. Patients were mostly White (93.4%) and female (76.3%), with a median age of 69 years (range, 19-96 years) and a median body mass index of 24.4 (range, 16.5-49.4). Through 8 weeks, 82.9% of patients (63/76; 95% CI, 72.5%-90.6%) experienced treatment success. Similarly, the rate of treatment success was 87.8% (36/41) in the subgroup of patients who received RBL after an antibiotic washout period > 72 hours. Treatment success rates ranged from 77-100% across patient subgroups, including those stratified by age and number of previous CDI episodes within the past 3 years (Table). Overall, 18 (23.7%) patients experienced an AE, 6 (7.9%) experienced a serious AE, and 1 (1.3%) experienced an AE of special interest (large bowel obstruction). AEs assessed as related to RBL occurred in 3 patients (3.9%). There was 1 fatal AE during the study, considered unrelated to RBL. Conclusion Initial results from ROAR are consistent with previous RBL trial results, indicating that RBL is effective and safe for preventing rCDI through 8 weeks after administration in real-world practice. Disclosures Nicholas W. Van Hise, PharmD, Ferring: Advisor/Consultant|Ferring: Grant/Research Support|Innoviva: Advisor/Consultant Teena Chopra, MD, MPH, Cepheid: Advisor/Consultant|Ferring Pharmaceuticals, Inc: Advisor/Consultant|Melinta: Speaker|Pfizer: Advisor/Consultant|Pfizer: Speaker|Shinogi: Speaker Kelly R. Reveles, PharmD, PhD, AstraZeneca: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant Sahil Khanna, MBBS, MS, Ferring Pharmaceuticals, Inc: Grant/Research Support|ProbioTech Inc: Advisor/Consultant|Rise: Advisor/Consultant|Takeda: Advisor/Consultant|Vedanta: Grant/Research Support Lasse Nielsen, MS, Ferring: Employee Lorien E. Urban, PhD, Ferring Pharmaceuticals Inc: Employee

Abstract Background The aim of this study was to evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA)—the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the US Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment. Methods PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered within 24–72 hours of antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success and sustained clinical response, at 8 weeks and 6 months after RBL administration, respectively. Results Overall, 793 participants were enrolled, of whom 697 received RBL. TEAEs through 8 weeks after administration were reported by 47.3% of participants; most events were mild or moderate gastrointestinal disorders. Serious TEAEs were reported by 3.9% of participants. The treatment success rate at 8 weeks was 73.8%; in participants who achieved treatment success, the sustained clinical response rate at 6 months was 91.0%. Safety and efficacy rates were similar across demographic and baseline characteristic subgroups. Conclusions RBL was safe and efficacious in participants with rCDI and common comorbidities. This is the largest microbiota-based live biotherapeutic study to date, and findings support use of RBL to prevent rCDI in a broad patient population. Clinical Trials Registration NCT03931941.