Largest Safety Evaluation of Microbiota-Based Therapeutic Reveals Rebyota's Positive Profile

This year has seen a flurry of approvals for the prevention of recurrent Clostridioides difficile infection (rCDI). Microbiota-based treatments, designed to restore a healthy gut microbiome, are proven to reduce rCDI incidence, but one study sought specifically to analyze the available safety data.

The study, published in Therapeutic Advances in Gastroenterology, provided cumulative safety data from 5 prospective clinical trials evaluating Ferring Pharmaceutical’s Rebyota (fecal microbiota, live-jslm; RBX2660). Rebyota was the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration (FDA) to prevent rCDI in adults.

“CDI is a serious illness that can lead to complications, including sepsis, colectomy, and death—the risks of which increase with each subsequent CDI recurrence,” wrote the study authors. They noted that the integrated safety analysis of Rebyota is the largest safety evaluation of any microbiota-based live biotherapeutic product to date, demonstrating that Rebyota “was optimized for patient safety through rigorous donor screening, standardized manufacturing protocols, and a noninvasive delivery mechanism.”

Rebyota is made of a broad consortium of live microbes from healthy human stool samples and administered rectally in 1 dose. The investigators examined Rebyota integrated safety analyses from 3 phase 2 trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and 2 phase 3 trials (PUNCH CD3, PUNCH CD3-OLS).

All trial participants were 18 years or older, had documented rCDI, and had completed standard-of-care antibiotic therapy before treatment with Rebyota. Assigned study treatment regimen was 1 or 2 doses of Rebyota or placebo, administered rectally.

In 4 of the 5 trials, participants with CDI recurrence within 8 weeks of receiving treatment or placebo were eligible to receive open-label Rebyota. Treatment-emergent adverse events were recorded for at least 6 months after last study treatment; adverse events and severe adverse events were collected through 12 months in the PUNCH CD2 trial and through 24 months in the PUNCH Open-Label trial.

In the 5 trials, 978 participants received at least 1 dose of Rebyota, either as their assigned treatment or open label after a CDI recurrence. There were 83 participants who only received placebo. Overall, treatment-emergent adverse events were reported in 60.2% of placebo only recipients and 66.4% of Rebyota only recipients.

Of all reported adverse events, only abdominal pain, nausea, and flatulence were higher in the Rebyota only group than in the placebo only cohort. Additionally, most treatment-emergent adverse events were mild to moderate in severity, and most were related to preexisting comorbidities. Potentially life-threatening treatment-emergent adverse events detected very infrequently, in 3.0% of all participants.

The study authors noted that there were no reported infections for which the causative pathogen was determined to be Rebyota. Across the 5 clinical trials, Rebyota was well tolerated in adults with rCDI. “In aggregate,” the study authors concluded, “these data consistently demonstrated the safety of [Rebyota].”