High Efficacy Marks for Investigational Treatment for C Difficile Infections

May 21, 2021
Kenny Walter

Kenny Walter is an editor with HCPLive. Prior to joining MJH Life Sciences in 2019, he worked as a digital reporter covering nanotechnology, life sciences, material science and more with R&D Magazine. He graduated with a degree in journalism from Temple University in 2008 and began his career as a local reporter for a chain of weekly newspapers based on the Jersey shore. When not working, he enjoys going to the beach and enjoying the shore in the summer and watching North Carolina Tar Heel basketball in the winter.

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.


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