Microbiome-based Therapeutic for C Difficile Demonstrates Extended Efficacy

An investigational microbiome-based therapeutic against C difficile was effective in reducing recurrence of infection for at least 3 months after administration, according to study findings reported at the 2020 American College of Gastroenterology (ACG) virtual meeting.

“The data presented at ACG show that the very promising efficacy seen with SER-109 at 8 weeks post-treatment is sustained out to 12 weeks post-treatment,” Bret Lashner, MD, Professor of Medicine, Cleveland Clinic, Cleveland, OH, and lead author of the study told Contagion®.

“They also show SER-109 had similar treatment benefits in both younger and older patients and regardless of antibiotic treatment,” Lashner added.

SER-109 is a microbiome-based therapeutic that delivers spores from the species Firmicutes. Although derived from the stool of health human donors, the manufacturing process yielding fractionated, purified Firmicute bacteria in spore form avoids concerns about undesirable bacterial or viral content, including of SARS-CoV-2, in transplanted fecal microbiota. The purified Firmicute spores are also resistant to gastric acid, facilitating an oral formulation.

The investigators had screened 281 patients at 75 sites in the US and Canada who were experiencing ≥3 unformed stools/day for ≥48 hours that tested positive for C. difficile toxin, to confirm, and distinguish active infection from colonization.

After completing a 10-21 day course of vancomycin or fidaxomicin, 182 subjects were randomized 1:1 to receive either 4 capsules of SER-109 daily for 3 days or matching placebo. The age, antibiotic use, and number or prior episodes were similar in both groups.

“Antibiotics targeted against C difficile bacteria are necessary, but insufficient to achieve a durable clinical response because they have no effect on C difficile spores that germinate within a disrupted microbiome,” Lashner and colleagues explained.

The early results at 8 weeks, previously reported in Contagion had demonstrated a statistically significant difference of 30.2% in the proportion of active treatment patients who had C difficile recurrence compared to those on placebo.The current results show that a similar difference in recurrence of infection between those receiving active treatment (16.7%) and placebo (48.7%) was maintained 12 weeks after treatment.

The results correspond to an absolute risk reduction of 31.1% (relative risk 0.35; 95% CI 0.21-0.58), which was consistent with results at 8 weeks. The measure of “sustained clinical response” was achieved in 88.9% of patients in the SER-109 group.

Subjects were stratified for analysis of treatment response in those younger than, and 65 years or older, with comparable results found in both age groups.Results were also similar regardless of the baseline antibiotic treatment.

The investigators reported that SER-109 continued to be well-tolerated in the extended study, with a safety profile similar to placebo.There were no serious adverse effects, and the most common treatment-emergent adverse effects were mild to moderate gastrointestinal disturbance.

“Recurrent C difficile is a very challenging condition to treat, and we’re glad to see additional confirmatory evidence of SER-109’s safety and efficacy,” Lashner said.“ By enriching for Firmicute spores, SER-109 achieved high efficacy, while mitigating risk of transmitting infectious agents.”

“Seres’ (Seres Therapeutics) ongoing open-label study in C diff will ideally provide the necessary safety database to ensure SER-109 licensure,” Lashner commented.