Scientific Poster Session IV - Original Research

Original Research
  Tuesday, November 14, 2023
  08:30 AM–10:00 AM

Abstract

Introduction: Antibiotics are often insufficient to treat recurrent Clostridioides difficile Infection (rCDI) because they have no effect on C. difficile spores, which germinate in a disrupted microbiome. Fecal microbiota spores, live-brpk (VOWST™; formerly SER-109; now VOS for Vowst Oral Spores) is an oral microbiota-based therapeutic designed to prevent rCDI in adults with a history of rCDI.

Research Question or Hypothesis: What is the overall safety/efficacy evidence for VOS?

Study Design: Integrated safety/efficacy analysis of ECOSPOR III (randomized, placebo-controlled) and ECOSPOR IV (open-label, single-arm).

Methods: ECOSPOR III enrolled 182 patients with history of =2 CDI recurrences; ECOSPOR IV enrolled 263 patients with rCDI. VOS was administered orally as 4 capsules over 3 consecutive days following antibiotic treatment. Treatment-emergent adverse events (TEAEs) were collected up to Week 8 following VOS therapy; serious TEAEs/adverse events of special interest were collected through Week 24. Efficacy endpoints were rCDI (toxin-positive diarrhea requiring treatment) through Week 8 and Week 24.

Results: In ECOSPOR III and ECOSPOR IV, 349 patients received at least 1 dose of VOS. Through Week 24, 221 (63.3%) patients experienced TEAEs, which were mostly mild to moderate and gastrointestinal in nature. The most common treatment-related TEAEs were flatulence, abdominal distension, abdominal pain, fatigue, and diarrhea. No study withdrawals were due to treatment-related TEAEs. No serious TEAEs or deaths were considered related to VOS by investigators. Among the 349 patients receiving VOS, 33 (9.5%; 95% CI, 6.6–13.0) and 53 (15.2%; 95% CI, 11.6–19.4) experienced on-study recurrence up to Week 8 and through Week 24, respectively. At Weeks 8 and 24, 90.5% (95% CI, 87.0–93.4) and 84.8% (95% CI, 80.6–88.4) of patients, respectively, were recurrence free.

Conclusion: This integrated analysis confirms VOS was well tolerated and rates of recurrence were low, supporting a role for microbiome restoration in prevention of rCDI.

Presenting Author

Sissi V. Pham PharmD
AESARA, Inc

Authors

David A. Lombardi PhD
Seres Therapeutics

Anne J. Gonzales-Luna PharmD
PLACEHOLDER

Elizabeth Hohmann MD
Infectious Diseases Division, Massachusetts General Hospital

Lisa von Moltke MD
Seres Therapeutics

Matthew D. Sims MD, PhD
Beaumont Hospital