SER-109 Scores High Efficacy Marks as a C Difficile Treatment

Barbara McGovern, MD

New data shows SER-109, an investigational, biologically derived microbiome treatment of purified Firmicute sports for the treatment of recurrent Clostridioides difficile infections (rCDI), could be viable, precedent setting option.

A team, led by Barbara McGovern, MD, VP Medical Affairs at Seres Therapeutics, presented interim analysis from the 287 patient ECOSPOR-III study in the ITT population at weeks 8 and 12.

C Difficile

C difficile infections are generally caused by the disruption of the microbiome coupled with exposure to C difficile spores. The leading risk for infections is the exposure of broad spectrum antibiotics, which can cause collateral damage to beneficial microbes that normally reside in the gastrointestinal microbiome.

In addition, there is a current lack of antibiotics that target C difficile due to a lack of effect on C difficile spores that germinate within a disrupted microbiome, preventing a sustained response in the majority of patients.

SER-109

The antibiotic targets for treating C difficile bacteria are currently insufficient and unable to produce a durable clinical response because they have no effect on C difficile spores that germinate within a disrupted microbiome.

“SER-109 represents a major paradigm shift in the clinical management of patients with recurrent CDI,” the authors wrote.

The Study

In the study, the investigators examined adult patients with rCDI of at least 3 episodes in the previous 12 months. The patients were screened at 75 sites in the US and Canada.

The investigators defined CDI as at least 3 unformed stools per day for less than 48 hours with a positive C difficile assay.

Each patient was treated with vancomycin or fidaxomicin for 10-21 days and the participants with symptom resolution were randomized to receive either SER-109 (4 capsules × 3 days) or matching placebo. The final analysis included 182 patients with a mean age of 65.5 years.

The patients were stratified by age and antibiotic received.

The investigators sought primary objectives of safety and efficacy at 8 weeks and primary efficacy endpoints of rCDI, defined as recurrent toxin+ diarrhea requiring treatment. They also sought secondary endpoints including efficacy at 12 weeks following dosing.

Results

A negative C difficile toxin assay was deemed the most common reason for screen failure.

However, SER-109 resulted in a lower proportion of patients with rCDI following dosing compared to placebo at week 8 (11.1% vs 41.3%, respectively; RR, 0.27; 95% CI, 0.15–0.51; P <0.001).

Efficacy rates were also significantly higher in the patients with the study drug in both stratified age groups—older or younger than 65 years.

The safety profile of SER-109 was similar to the placebo, with the most common treatment-emergent adverse events being mainly mild-to-moderate gastrointestinal symptoms.

These adverse events were not considered serious and did not lead to infections, deaths, or drug discontinuations related to SER-109.

“SER-109, an oral live microbiome therapeutic, achieved high rates of sustained clinical response with a favorable safety profile,” the authors wrote. “By enriching for Firmicute spores, SER-109 achieves high efficacy while mitigating risk of transmitting infectious agents, beyond donor screening alone.”

The study, “Efficacy and Safety of Investigational Microbiome Drug SER-109 for Treatment of Recurrent Clostridioides difficile Infection,” was published online in Antimicrobial Stewardship & Healthcare Epidemiology.