Efficacy of Fecal Microbiota Therapy for Recurrent Clostridioides difficile Infection

The phase 3 PUNCH CD3 Open-Label Study, examined the efficacy and safety of Fecal Microbiota, Live (RBL), the first FDA-approved microbiota-based live biotherapeutic product, in individuals receiving concomitant medications associated with gut dysbiosis.

Paul Feuerstadt, MD, FACG, AGAF an associate clinical professor of medicine at the Yale School of Medicine. He serves as an attending gastroenterologist at The Pact Gastroenterology Center, in the realm of microbiome research. Feuerstadt's focus areas include CDI, eosinophilic gastrointestinal disorders, and intestinal ischemic disorders.

“RCDI involves 2 phases," explains Feuerstadt. "The vegetative phase causes symptoms, while the spore phase leads to recurrence."

Participants, aged 18 years and older with documented rCDI, received a single rectal dose of RBL within 24-72 hours of completing standard-of-care antibiotics. Among the subgroups taking proton pump inhibitors (PPIs), statins, and/or psychotropic medications, treatment success rates at 8 weeks were consistent with the overall population, indicating a success rate of approximately 74.6%.

“Efficacy was consistent across 483 patients that received RBL in an open-label format, and 42.1% of them received PPIs, 48.6% received the statin medications, and 55.2% received the psychoactive medications,” according to Feuerstadt. “But when we focused in on that 8-week efficacy, it was very consistent with the open-label study data as well as the phase 3 data overall efficacy, and the group that was on PPIs was 77%, 75.9% in those that were on statins, and 73.8% in those who were receiving psychoactive medications."

Further analysis revealed comparable treatment success rates for participants concurrently using 1, 2, or 3 or more of these medications. The overall incidence of treatment-emergent adverse events (TEAEs) among those taking PPIs, statins, and psychotropic medications was within the range of 59.8% to 66.9%, with most events being mild or moderate gastrointestinal disorders.

“The open-label study from RBL essentially showed patients with IBS respond similarly, patients with inflammatory bowel disease, ulcerative colitis, Crohn's disease, microscopic colitis, these are the things that we see in clinical practice,” according to Feuerstadt. “Open-label study opened these doors for us as clinicians to say this is both safe and effective.”

Notably, serious TEAEs occurred in a minority of participants and were deemed unrelated to RBL administration. This suggests that RBL remains efficacious and safe in individuals taking common non-antibiotic medications associated with dysbiosis and rCDI, mirroring outcomes observed in the broader PUNCH CD3-OLS population. These findings underscore the potential of RBL as a viable preventive measure against rCDI following standard antibiotic treatment, even in the presence of medications known to impact gut microbiota.

“The safety is very consistent with this product,” according to Feuerstadt. “So, there is no real major concerning safety signals that we have seen even in the specialized populations.”

Reference

Feuerstadt P, Tillotson G, Carlson T, et. al. Efficacy and Safety of Fecal microbiota, live-JSLM in Participants with Recurrent Clostridioides difficile Infection Receiving Concomitant Medications. Digestive Disease Week (DDW). May 18-21, 2024 Washington DC.