Regulatory Decision Summary for Rebyota

The purpose of the current new drug submission is to request authorisation of Rebyota for the prevention of recurrence of Clostridioides difficile infection (CDI) in adults following antibiotic treatment for recurrent CDI.

Rebyota is a fecal microbiota suspension prepared from human stool from pre-screened and qualified donors, supplied as a pre-packaged single dose 150 mL faecal microbiota suspension for rectal administration.

Efficacy of Rebyota:

Rebyota’s efficacy was assessed in two randomized, double-blind, placebo-controlled, multicenter Phase 3 and Phase 2 studies. Adults aged 18 and older with recurrent Clostridioides difficile infection (CDI), defined by multiple episodes of diarrhea and positive stool tests for C. difficile toxin, were enrolled. Participants were required to have completed at least 10 days of antibiotic therapy and have controlled CDI symptoms before treatment.

• The treatment success rate (defined as absence of CDI diarrhea within 8 weeks post-treatment) was 70.6% for Rebyota versus 57.5% for placebo, showing a 13.1% higher success rate for the treatment group

• “Sustained clinical response”, defined as continued absence of CDI for 6 months post-treatment, was 65.5% in the Rebyota group versus 56.5% in the placebo group.

Safety of Rebyota:

Safety was evaluated across five clinical studies, including the two randomized trials (Study 1 and Study 2) and three open-label studies. A total of 978 adults with a history of recurrent CDI were enrolled, with 595 receiving a single dose of Rebyota.

• Adverse events: The most common adverse reactions associated with Rebyota (reported in ≥3% of participants and more frequently than in placebo recipients) were abdominal pain (8.9%), diarrhea (7.2%), abdominal distention (3.9%), flatulence (3.3%), and nausea (3.3%). These occurred most frequently in the first 2 weeks after treatment. Most adverse reactions were mild to moderate in severity.

• Serious adverse events: In a pooled analysis, 10.1% of Rebyota recipients reported serious adverse events within 6 months of treatment, compared to 7.2% in the placebo group. None of these were considered related to the investigational product.

In conclusion, Rebyota demonstrated superior efficacy, albeit modest, compared to placebo in treating recurrent CDI, with a favorable safety profile, mostly involving mild to moderate adverse events.

For further details about Rebyota, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.