SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons...

Area of Science:

• Microbiome therapeutics
• Gastroenterology
• Infectious diseases

Background:

• Recurrent C. difficile infection (rCDI) is linked to reduced microbial diversity and lower levels of secondary bile acids, which normally inhibit C. difficile.
• SER-109, an investigational microbiome drug composed of purified bacterial spores, has shown potential in reducing rCDI in prior studies.

Purpose of the Study:

• To evaluate the efficacy and safety of SER-109 in patients with multiple episodes of rCDI.
• To assess the impact of SER-109 on C. difficile recurrence, microbial engraftment, and bile acid profiles.

Main Methods:

• A Phase 2, double-blind trial randomized patients with resolved rCDI to SER-109 or placebo.
• Patients were stratified by age (<65 or ≥65 years).
• Outcomes included safety, C. difficile recurrence rates, SER-109 engraftment, and changes in bile acid concentrations.

Main Results:

• SER-109 showed a trend toward reduced rCDI compared to placebo (44.1% vs 53.3%), but did not reach statistical significance overall.
• A significant reduction in recurrence was observed in patients aged 65 and older (45.2% vs 80%).
• Early engraftment of SER-109 was associated with nonrecurrence and increased secondary bile acids.

Conclusions:

• Early engraftment of SER-109 was linked to decreased CDI recurrence and demonstrated a favorable safety profile.
• The Phase 2 dosing may have been suboptimal, leading to adjustments in the ongoing Phase 3 trial, including higher SER-109 doses and mandatory toxin testing for diagnosis.