High Efficacy Marks for Investigational Treatment for C Difficile Infections

Kenny Walter

SER-109 resulted in a 73% reduction in relative risk for CDI over 8 weeks.

In data presented during the 2021 Digestive Disease Week (DDW) Virtual Meeting, an investigational treatment for Clostridium difficile infections (CDI) resulted in a substantial decrease in relative risk.

A team, led by Louis Korman, MD, Capital Digestive Care, tested an investigational microbiome therapeutic consisting of purified Fimicutes spores called SER-109, over the course of a 24-week study as a therapeutic that reduces the risk of developing c difficile infections at 75 sites in the US and Canada.

The current stable of antibiotics targeting C difficile bacteria are considered insufficient to achieve a durable clinical response because they have no effect on c difficile spores that germinate within a disrupted microbiome.

The Trial

In the phase 3 randomized controlled trial, the researchers examined 287 adult patients with recurrent CDI and found SER-109 results in a 73% relative risk reduction at week 8 when compared to placebo (11.1% vs 41.3%, respectively; P <0.001).

Each patient included in the final analysis suffered from at least 3 recurrent CDI episodes on the proceeding 12 months. CDI was defined at least 3 unformed stools per day for at least 48 hours with a positive C difficile assay.

Following completion of a 10-21 regimen of vancomycin or fidaxomin, each patient with symptom resolution was equally randomized to receive 4 capsules every 3 days of SER-109 or a match placebo. The patients were also stratified by age and antibiotic received.

Endpoints

The investigators sought primary objectives of safety and efficacy of the treatment at 8 weeks and primary efficacy endpoints of rCDI (recurrent toxin+ diarrhea requiring treatment). They also sought secondary endpoints of efficacy and safety at 24 weeks after dosing.

Of the 287 patients screened, 182 were randomized for the final analysis, with a mean age of 65.5 years old.

The most common reason for screen failure was a negative C. difficile toxin assay, while there was a significantly lower proportion of SER-109 subjects had rCDI compared to placebo at week 24 (20.0% vs 49.9%, respectively; RR, 0.41; 95% CI 0.26-0.65; P <0.001).

Safety Profile

The researchers also found the treatment was well-tolerated, with a safety profile similar to placebo.

There were some treatment-emergent adverse events, which were mainly mild-to-moderate gastrointestinal symptoms. There were no serious treatment-emergent adverse events, infections, deaths, or drug-related discontinuations related to SER-109.

“SER-109, an oral live microbiome therapeutic, maintained durable efficacy over 24 weeks after dosing with a safety profile comparable to placebo,” the authors wrote. “By enriching for Firmicute spores, SER-109 achieves high efficacy, while mitigating risk of transmitting infectious agents and represents a major paradigm shift in the clinical management of patients with recurrent CDI. An open-label study for patients with recurrent CDI is currently enrolling.”

The study, “24-WEEK EFFICACY AND SAFETY DATA FROM ECOSPOR-III, A PHASE 3 DOUBLE-BLIND, PLACEBO-CONTROLLED RANDOMIZED TRIAL OF SER-109, AN INVESTIGATIONAL MICROBIOME THERAPEUTIC FOR TREATMENT OF RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION,” was published online by DDW.