11 - Significant and Durable Microbiome Restoration in a Phase 3 Trial of Fecal Microbiota, Live-JSLM for Recurrent Clostridioides difficile Infection When Administered by Colonoscopy

Sahil Khanna, MBBS, MD, MS¹, Paul Feuerstadt, MD, FACG², Daniel Van Handel, MD³, Ken Blount, PhD⁴, Tonya Ward, PhD⁴, Beth Adamowicz, PhD⁴
1Mayo Clinic Rochester, Rochester, MN; 2Yale University School of Medicine and PACT-Gastroenterology Center, Hamden, CT; 3Plymouth Endoscopy Center & Clinic, Plymouth, MN; 4Ferring Pharmaceuticals, Roseville, MN

Introduction: Microbiota-based products may shift the microbial composition of a recipient’s gut microbiome to suppress Clostridioides difficile outgrowth and prevent recurrent C. difficile infection (rCDI). Fecal microbiota, live-jslm (RBL) is the first FDA-approved, single-dose, microbiota-based product indicated for the prevention of rCDI in adults after standard-of-care antibiotic therapy. The safety and clinical effectiveness of RBL when administered by colonoscopy to adults with rCDI was evaluated in CDI-SCOPE (NCT05831189), a phase 3b multi-center, single-arm trial. Microbiome composition, diversity of bacterial populations, and the Microbiome Health Index for post-Antibiotic dysbiosis (MHI-A) were assessed among RBL recipients in CDI-SCOPE.

Methods: These exploratory analyses included samples from 41 participants who received RBL in CDI-SCOPE. Treatment success was defined as the absence of Clostridioides difficile infection (CDI) diarrhea for 8 weeks after RBL administration. Participants were required to provide stool samples prior to bowel preparation and RBL administration by colonoscopy (baseline), at regular follow-up visits after 1, 4, and 8 weeks, after 3 and 6 months, and at the time of CDI recurrence within 8 weeks of RBL administration. Samples were extracted and sequenced using deep ( >20 MM reads) shotgun methods. Class-level relative abundances and alpha diversity were evaluated, including the MHI-A — a microbiome biomarker of post-antibiotic dysbiosis and restoration.

Results: Overall, 41 received RBL via colonoscopy; 39 participants completed an 8-week visit, with a treatment success rate of 95%.There were 20 participants with a full stool sample timeline (baseline, 1 week, 4 weeks, 8 weeks, 3 months, and 6 months) and 18 with a baseline sample and at least 1 post-administration sample. Compared with baseline, microbiome composition and MHI-A shifted significantly towards RBL composition among responders. Bacteroidia and Clostridia increased in abundance, whereas Gammaproteobacteria and Bacilli decreased following RBL administration via colonoscopy (Figure 1). MHI-A also increased from baseline to 6 months after RBL administration (Figure 2).

Discussion: RBL administered via colonoscopy restored microbiome composition concurrent with clinical response. These restorative changes reflect shifts from a post-antibiotic state of dysbiosis to a healthier state characterized by increased colonization resistance.


Figure: Figure 1. Relative abundance of key genera over time in treatment responders in CDI-SCOPE.


Figure: Figure 2. Microbiome Health Index for post-Antibiotic dysbiosis (MHI-A) values over time in treatment responders in CDI-SCOPE.

Disclosures:
Sahil Khanna: Ferring Pharmaceuticals – Advisor or Review Panel Member. Finch Therapeutics – Grant/Research Support. Immuron Limited – Consultant. Jetson Probiotics – Stock Options. Niche Pharmaceuticals – Consultant. Rebiotix – Grant/Research Support. Seres Therapeutics – Grant/Research Support. Vedanta BioSciences – Grant/Research Support.
Paul Feuerstadt: Ferring Pharmaceuticals – Advisor or Review Panel Member, Honoraria. Rebiotix, Inc. – Consultant. Seres Therapeutics – Advisor or Review Panel Member, Honoraria. Takeda Pharmaceuticals – Advisor or Review Panel Member, Consultant, Honoraria.
Daniel Van Handel: Ferring Pharmaceuticals – Speakers Bureau.
Ken Blount: Ferring Microbiome, Inc. – Employee.
Tonya Ward: Ferring Microbiome, Inc. – Employee.
Beth Adamowicz: Ferring Microbiome, Inc. – Speakers Bureau.

Sahil Khanna, MBBS, MD, MS¹, Paul Feuerstadt, MD, FACG², Daniel Van Handel, MD³, Ken Blount, PhD⁴, Tonya Ward, PhD⁴, Beth Adamowicz, PhD⁴, 11, Significant and Durable Microbiome Restoration in a Phase 3 Trial of Fecal Microbiota, Live-JSLM for Recurrent Clostridioides difficile Infection When Administered by Colonoscopy, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.