Phase 3b Trial Shows Colonoscopic Administration of Rebyota Effective for Preventing Recurrent C. difficile Infection
核心洞察
A phase 3b clinical trial demonstrated that Rebyota (fecal microbiota, live-jslm) administered via colonoscopy achieved a 95.1% treatment success rate in preventing recurrent C. difficile infection (搜索).
Only 9.8% of participants experienced Rebyota-related adverse events, all of which were mild and gastrointestinal in nature, confirming the safety profile of this administration method.
Patients reported significant quality of life improvements after treatment, with 89.7% experiencing symptom relief within the first month and substantial reductions in diarrhea, abdominal pain, and fatigue.
Ferring Pharmaceuticals has announced promising results from its Phase 3b CDI-SCOPE clinical trial evaluating the safety and effectiveness of REBYOTA® (fecal microbiota, live-jslm) when administered via colonoscopy for preventing recurrent Clostridioides difficile (搜索) infection (rCDI (搜索)). The findings, presented at Digestive Disease Week (DDW) 2025 in San Diego, demonstrate a new potential administration method for this first-in-class microbiome-based therapy.
The multi-center, single-arm study enrolled 41 adults with a history of rCDI (搜索) who had recently completed standard antibiotic therapy. Participants received a single 150-mL dose of REBYOTA delivered to the right side of the colon through colonoscopy, rather than the FDA-approved rectal administration method.
Safety and Efficacy Results
Treatment success, defined as the absence of CDI recurrence within 8 weeks, was observed in 39 participants (95.1%). Two participants (4.9%) withdrew consent and had indeterminate outcomes.
The safety profile was favorable, with REBYOTA-related treatment-emergent adverse events (TEAEs) reported in only four participants (9.8%). All of these events were mild in intensity and related to the gastrointestinal tract. Overall, 18 participants (43.9%) experienced a total of 33 TEAEs, with most categorized as mild (75.8%) or moderate (15.2%). No serious events resulted in intensive care or death.
"Colonoscopies are routinely used by physicians managing patients with recurrent C. difficile infection (搜索)," said Dr. Paul Feuerstadt, M.D., F.A.C.G., A.G.A.F., Yale School of Medicine and PACT-Gastroenterology Center (搜索), a lead investigator of CDI-SCOPE. "The insights gained from this investigative study point to administration via colonoscopy as a promising potential option for physicians to consider for their patients."
Impact on Patient Quality of Life
A secondary analysis from the CDI-SCOPE study reported significant improvements in health-related quality of life (HRQoL) following treatment. Prior to REBYOTA administration, all participants reported that CDI recurrence severely impacted their daily living, including disrupting sleep and forcing them to remain near bathrooms at all times. Most participants also reported that rCDI (搜索) affected their social life and relationships (96.7%) and emotional wellbeing (93.3%).
Following treatment, 89.7% of participants experienced symptom improvement within the first month, with more than half (51.7%) feeling better within the first week. Symptom severity ratings (on a scale of 0-10) decreased dramatically at Week 8 for diarrhea (from 8.9 to 1.3), abdominal pain (from 7.5 to 1.6), and fatigue (from 8.1 to 1.7).
"Recurrent CDI is a life-altering condition that many patients in our CDI-SCOPE trial called 'a literal living nightmare' that makes it impossible to function," said Raza Ahmed, MD, Senior Director of Medical Affairs, Ferring Pharmaceuticals. "We are proud that REBYOTA has become an important therapy for many patients who, for too long, were stuck in an agonizing cycle of CDI recurrence."
Physician Experience with Colonoscopic Administration
The study also assessed physician experience with the colonoscopic administration procedure. Among investigators, 90.2% reported a positive or very positive experience across all aspects of administration, including material preparation time and ease of passage through the colonoscope. All 39 patients who completed 8-week visits were assessed by physicians as either "much improved" or "very much improved" on the clinical global impression-improvement scale (CGI-I).
Dr. Feuerstadt explained the technical aspects of the procedure: "If instead of administering via the tube, we use an off-label usage where we cut the bag open, we draw it up into 350 cc syringes, we do a colonoscopy and administer to the right colon, and then allow peristalsis to propulse the material throughout the colon, that might potentially be a more effective way to administer this."
Patient Demographics and Treatment History
The open-label study enrolled patients with at least one recurrence of CDI. The average participant age was 61.2 years, with most being women (88%) and White (95%). Of the participants, 43.9% had experienced their first CDI recurrence, and 63% had received vancomycin as their standard of care antibiotic treatment.
Additional PUNCH™ Clinical Program Data
Ferring also presented additional analyses from its broader PUNCH™ clinical trial program at DDW 2025, including:
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An integrated safety analysis of five clinical trials (n=1192) demonstrating a favorable safety profile with REBYOTA across all trials in the development program, including in participants with inflammatory bowel disease (IBD) and immunocompromising comorbidities.
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An exploratory analysis of the PUNCH™ CD3 trial showing that improvements in quality of life were associated with changes in microbiome composition. Patients who responded to REBYOTA had a healthier gut microbiome with increased relative abundance of beneficial gut microbiota (Bacteroidia (搜索) and Clostridia (搜索)) and decreased levels of other bacteria (Gammaproteobacteria and Bacilli).
Clinical Implications
"Several centers, since Rebyota was FDA approved, have been doing this consistently, but we really didn't have a codified format for this," Dr. Feuerstadt noted. "This should allow local providers, local clinicians, the comfort to say, if I'm a gastroenterologist and I think colonoscopy is appropriate for a patient, it's safe for a patient, this might be a very effective and safe method to use to prevent recurrent C difficile."
The findings may support broader adoption of colonoscopic administration as an alternative to the FDA-approved rectal delivery method. Dr. Feuerstadt emphasized that providing multiple administration options could improve patient access to this important therapy.
"When we think about colonoscopic administration of Rebyota, this is just another method," he concluded. "Patients should have access to these heroic measures breaking that cycle of recurrence that so many patients with C difficile go through. If there's another option that patients are more comfortable doing, then that means patients have more access and better availability, and ultimately improving outcomes in a safe and effective way."
REBYOTA is currently FDA-approved for the prevention of recurrent C. difficile infection (搜索) in individuals 18 years of age and older, following antibiotic treatment for recurrent C. diff infection. The colonoscopic administration method explored in this study represents an investigational, off-label use of the approved therapy.