Colonoscopic administration of fecal microbiota live-jslm (Rebyota or RBL) has demonstrated remarkable efficacy in preventing recurrent Clostridioides difficile infection (rCDI) in adults, according to new phase 3b trial results presented at Digestive Disease Week 2025.
The open-label CDI-SCOPE study, conducted across 12 US clinical sites, reported a 95.1% treatment success rate among 41 adult participants with a history of rCDI. Investigators observed minimal adverse events, with most side effects being mild and limited to gastrointestinal symptoms.
"This approach represents a significant advancement in how we manage recurrent C. difficile infections," said Paul Feuerstadt, MD, lead investigator of the study. "By offering a more structured and accessible microbiota restoration technique, we're improving upon older fecal transplant approaches that were often less standardized and more difficult to implement in clinical practice."
High Physician Satisfaction Rates
The trial also assessed physician feedback regarding the colonoscopic administration procedure. Over 90% of physicians reported high satisfaction with both the procedure itself and subsequent patient outcomes, suggesting strong clinical acceptance of this delivery method.
Colonoscopic administration involves delivering the microbiota-based therapeutic directly to the colon during a standard colonoscopy procedure, allowing for precise placement of the therapeutic agent. This method ensures the microbial communities reach their target location intact, potentially enhancing therapeutic efficacy.
Addressing a Significant Clinical Challenge
Recurrent C. difficile infection represents a substantial clinical challenge, with approximately 25% of patients experiencing at least one recurrence after initial treatment. Each subsequent recurrence further increases the risk of additional episodes, creating a difficult cycle for patients and clinicians.
The microbiota-based approach works by restoring diversity to the gut microbiome, which is typically disrupted by antibiotic use and C. difficile infection. By reintroducing a complex community of beneficial bacteria, the therapy helps reestablish colonization resistance against C. difficile.
"What's particularly encouraging about these results is that we're seeing such high success rates with a single administration," Feuerstadt noted. "For patients who have experienced multiple recurrences and cycles of antibiotics, this represents a potential pathway to breaking that recurrence cycle."
Safety Profile and Patient Experience
The safety profile observed in the CDI-SCOPE trial aligns with previous studies of microbiota-based therapeutics for rCDI. Most adverse events were transient and included mild gastrointestinal symptoms such as abdominal discomfort, bloating, and changes in bowel habits.
Importantly, no serious adverse events attributed to the therapy were reported during the study period. This favorable safety profile, combined with the high efficacy rate, positions colonoscopic administration of RBL as a promising option for patients with rCDI.
Clinical Implications and Future Directions
The successful results from this phase 3b trial add to the growing body of evidence supporting microbiota-based approaches for managing rCDI. As one of the first standardized microbiota-based therapeutics to receive regulatory approval, Rebyota represents an important advancement in the field.
The colonoscopic administration route may offer advantages over other delivery methods, particularly for patients who have failed previous treatments or who have anatomical considerations that make other approaches challenging.
"These findings suggest that colonoscopic administration should be considered a viable and effective option for delivering microbiota-based therapeutics," said Feuerstadt. "The high success rates and positive physician feedback indicate this approach could become an important part of our clinical arsenal against recurrent C. difficile infection."
Researchers plan to conduct further studies to evaluate long-term outcomes and to identify specific patient populations who might particularly benefit from this administration route. Additionally, ongoing research is exploring the potential applications of microbiota-based therapeutics for other gastrointestinal conditions characterized by microbiome disruption.
As microbiota-based therapeutics continue to evolve, the CDI-SCOPE study provides valuable evidence supporting colonoscopic administration as an effective delivery method that may help optimize treatment outcomes for patients suffering from this challenging and recurrent infection.
