FDA Panel Votes on Microbiota-Based Enema Therapy for Recurrent Clostridioides Difficile Infection

The Food and Drug Administration (FDA)’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 13 “yes” and 4 “no” on the question of whether the available evidence supports the approval of RBX2660, a microbiota-based live biotherapeutic, to reduce recurrence of Clostridioides difficile infection (CDI) after antibiotic treatment.

RBX2660 delivers human-derived microbes via an enema into a patient’s intestinal tract. Studies have shown that most CDI cases occur after antibiotics disrupt the normal gastrointestinal flora. The clinical development program for RBX2660 included 6 studies with a total of 1061 patients, of which 978 were treated with RBX2660.

The application included data from the pivotal phase 3 PUNCH CD3 (ClinicalTrials.gov Identifier: NCT03244644) and phase 2 PUNCH CD2 (ClinicalTrials.gov Identifier: NCT02299570) trials, which compared the efficacy and safety of RBX2660 to placebo in patients 18 years of age and older who had CDI recurrence after a primary episode of CDI. The primary endpoint was the absence of C. difficile diarrhea without the need for retreatment at week 8. Treatment success was defined as the absence of CDI diarrhea through 8 weeks.

Results using the modified intent-to-treat population showed that RBX2660 met the primary endpoint demonstrating superior treatment success compared with placebo, 71% vs 57%, respectively (treatment difference, 13%; 95% CI, 0.02-0.24). RBX2660 demonstrated a 99.1% posterior probability of superiority to placebo, which met the 97.5% minimum threshold. 

The safety profile of RBX2660 was comparable to placebo. The majority of treatment emergent adverse events for RBX2660 were mild to moderate in nature and were similar to placebo. The most frequently reported adverse events from day 1 to day 7 were flatulence, abdominal distention, and abdominal pain.

The panel voted 12 to 4 with 1 abstention that the data were adequate to support the safety of RBX2660 when administered to adults 18 years of age and older following antibiotic treatment for recurrent CDI.

Although not bound by the committee’s recommendations, the FDA does take them into consideration when making decisions on approval.

This article originally appeared on MPR