Retrospective Analysis of the Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTATM) Administered Under Enforcement Discretion to Patients With Clostridioides difficile Infection

Abstract

Background Fecal microbiota, live-jslm (FMBL; REBYOTA™), the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration used to prevent recurrent Clostridioides difficile infection (rCDI) in adults, has been evaluated in 5 prospective clinical trials. A retrospective analysis considered the safety and efficacy of FMBL administered under US Food and Drug Administration enforcement discretion to patients with rCDI and broad eligibility criteria mimicking real-world practice. Methods We retrospectively identified adults with rCDI treated with FMBL under enforcement discretion between November 1, 2015, and September 30, 2019, across 5 study sites. CDI diagnosis was based on site-specific practice. The primary safety set (PSS) included all patients who were naïve to previous FMBL treatment and had continuously comprehensive medical records for 6 months following treatment. Results The primary treatment cohort had 94 patients; the PSS included 64 patients with common comorbidities receiving diverse chronic therapeutics. Most treatment-emergent adverse events were mild to moderate in severity and comparable between comorbidity subgroups and the overall population. There were no serious adverse events related to FMBL or the administration procedure. In the PSS, 82.8% of FMBL-treated patients responded at 8 weeks, of whom 88.7% had sustained response through 6 months. The number of FMBL doses administered had no marked effect on outcome. Conclusions Together with prospective clinical trial outcomes, these findings support the efficacy and safety of FMBL to prevent rCDI, with diagnostics and comorbidities representative of real-world clinical practice.

Prescription Microbiome Therapeutic for Recurrent Clostridioides difficile Infection: Fecal Microbiota Live-jslm

“…Use of RBL for fulminant CDI should only be considered after discussion within a multidisciplinary team considering risk, benefits, and documentation of informed consent, given this off-label indication. Endoscopic delivery of this product would also be offlabel, but the experience using FMT through this route suggests practitioners' comfort and procedural safety (23). A clinical trial assessing safety and efficacy colonoscopic delivery of RBL is underway [NCT05831189].…”

Review article: The epidemiology and management of Clostridioides difficile infection—A clinical update

“…The first, faecal microbiota live‐jslm or REBYOTA (RBL), was approved by the FDA in November 2022 and is administered rectally as a single 150 mL dose within 24–72 h following completion of anti‐CDI antibiotics 103 . This is a donor derived whole consortium product that is required to meet various quality metrics through an extensive screening process 104–107 . A pivotal phase III randomised double‐blind placebo‐controlled trial of patients with recurrent CDI, PUNCH CD3, with a Bayesian analysis incorporating prior phase IIb data, found an 8‐week clinical response rate of 70.6% with faecal microbiota live‐jslm compared to 57.5% with placebo (13.1% treatment effect) 106 .…”

Bring it on again: antimicrobial stewardship in transplant infectious diseases: updates and new challenges

“… 19 Rebyota®, the first FDA-approved fecal microbiota product, is another encouraging therapeutic advancement, though data specific to transplant recipients are minimal. 20 As data emerge to clarify candidate selection criteria and long-term outcomes, the relationship between fecal microbiota therapies and antimicrobial stewardship is an evolving area of interest.…”