In a recent study published in the Open Forum Infectious Diseases journal, researchers assessed the safety and efficacy of fecal microbiota, live-jslm (FMBL), in preventing Clostridiodes difficile infection (CDI).
Study: Retrospective Analysis of the Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTA™) Administered Under Enforcement Discretion to Patients with Clostridioides difficile Infection. Image Credit: TopMicrobialStock/Shutterstock.com
Background
C. difficile is a leading cause of mortality in healthcare-related infections in the United States (US). CDI and recurrent CDI (rCDI) cause substantial morbidity and mortality.
Antibiotics are the standard of care (SOC) treatment for CDI and rCDI. Nonetheless, the likelihood of rCDI increases after each episode of CDI, underscoring the need for novel therapies to prevent rCDI.
Fecal microbiota transplantation (FMT) is recommended for rCDI patients unresponsive to SOC therapy. The clinical response rate for FMT in rCDI patients was 92% across 37 studies, many of which were retrospective case series.
However, there is a lack of standardized study designs, methodologies, formulations, and endpoints, which might make it challenging to interpret FMT's safety and efficacy.
FMBL is the first microbiota-based single-dose live biotherapeutic to prevent CDI recurrence in adults (18 years or older). It is manufactured from human feces sourced from qualified donors. So far, five prospective clinical trials have demonstrated consistent efficacy and safety of FMBL in rCDI patients.
About the study
In the present study, researchers retrospectively evaluated the efficacy and safety of FMBL administered under the enforcement discretion (ED) policy of the US Food and Drug Administration (FDA) in CDI patients between November 2015 and September 2019. The main objective was to investigate the tolerability and safety of FMBL in six months following treatment.
The study's primary endpoint was the number of subjects with treatment-emergent adverse events (TEAEs) related to the procedure or FMBL.
Other endpoints were the number of TEAEs of particular interest, adverse events (AEs) per patient, TEAE severity, new onset of chronic conditions, and exacerbation of pre-existing conditions. Secondary objectives were the evaluations of FMBL efficacy against rCDI in eight weeks of treatment and sustained response for six months post-treatment.
Safety and efficacy were analyzed for three populations. The full analysis set (FAS) comprised all patients meeting the eligibility criteria who received FMBL under ED. The primary safety set (PSS) had FMBL-naïve patients with comprehensive medical records for six months before treatment.
The secondary safety set (SSS) included patients ruled out from the PSS due to FMBL treatment in a prior study, the lack of comprehensive medical records, or early exit. Treatment success was the non-occurrence of rCDI within eight weeks after the final FMBL dose. The sustained response was the absence of a CDI event within six months after the last dose.
Findings
The study comprised 94 patients, with an average age of 59.8 years. Sixteen patients received FMBL doses in prior clinical studies, and 15 had incomplete medical records; these patients were excluded from the PSS.
A single course of treatment in the PSS included one or two doses of FMBL. Patients with CDI recurrence after the first treatment might have received an additional treatment course. There were 144 TEAEs recorded in 62.5% of FMBL-treated patients. They were FMBL-related in 17% of patients and procedure-related in 4.7%.
Most TEAEs (92%) were mild/moderate. Several patients (12%) experienced serious TEAEs, and 7.8% developed severe life-threatening AEs, although none were related to FMBL/procedure. Around 35% of patients experienced TEAEs of particular interest. Pre-existing conditions were exacerbated in 20% of patients.
New-onset chronic conditions were recorded in 3% of patients. Patients with gastrointestinal and non-specific inflammation at baseline had more serious TEAEs.
Still, the incidence of FMBL/procedure-related TEAEs was similar between the overall sample and comorbidity sub-groups. More than 82% of patients in the PSS achieved FMBL treatment success, with similar success rates in patients who received one or two FMBL doses. Over 88% of patients showed a sustained clinical response, with comparable rates between one- and two-dose recipients.
Unknown treatment outcomes were recorded for eight patients in the FAS and were deemed treatment failures. As such, treatment success was achieved in 70% of FAS patients. The number of FMBL doses had no meaningful effect on treatment outcomes. Approximately 88% of FAS patients showed a sustained clinical response.
Conclusions
In the first eight weeks after administration, FMBL demonstrated high clinical efficacy against CDI recurrence. A significant proportion of responders showed a sustainable clinical response.
The findings corroborate the potential safety and efficacy of FMBL in real-world patient populations with common comorbid conditions representative of clinical practice.
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