SER-109 Reduces Risk of Recurrence of C Difficile Infections

Paul Feuerstadt, MD

An investigational live microbiome therapeutic continues to show positive results in treating patients with recurrent clostridium difficile infections (CDI).

A team, led by Paul Feuerstadt, MD, Yale University School of Medicine, New Haven, recently released phase 3 data showing SER-109 resulted in a significant reduction in CDI recurrence in comparison to placebo.

SER-109

SER-109 is an investigational microbiome therapeutic designed to address the disrupted microbiome that supports C difficile spore germination into toxic producing bacteria. The treatment is composed of purified Firmicutes spores.

“Clinical outcomes in recurrent C. difficile infection may be improved by using a two-pronged treatment approach: antibiotics to kill toxin-producing bacteria followed by a microbiome therapeutic to inhibit C. difficile spore germination and bacterial replication through microbiome repair,” the authors wrote.

The Trial

In the phase 3, double-blind, randomized, placebo-controlled study, the investigators examined 182 patients with 3 or more episodes of CDI. Each participant received either SER-109 or placebo, 4 capsules daily of each for 3 days, following standard-of-care antibiotic treatment. The mean age of the study population was 65.5 years.

The investigators sought primary efficacy outcomes of superiority of SER-109 to placebo in reducing the risk of C difficile infection recurrence up to 8 weeks after treatment.

The team performed toxin testing for diagnostic reasonings at baseline and then stratified participants according to age and antibiotic agent received. They also performed analysis of safety, microbiome engraftment, and metabolites.

Positive Efficacy

The results show the primary efficacy objective was met and SER-109 was deemed superior to placebo.

Overall, only 12% of the SER-109 group had a recurrence of CDI, compared to 40% of the placebo group (RR, 0.32; 95% CI, 0.18-0.58; P <0.001 for a relative risk of <1.0; P <0.001 for a relative risk of <0.833).

The majority of recurrence events occurred as early as day 4 after randomization, with 75% (n = 36) occurring within 2 weeks and 85% (n = 41) occurring within 4 weeks of administration of SER-109 or placebo.

Looking at the stratified groups, the investigators found the study drug led to less frequent recurrence (RR, 0.24; 95% CI, 0.07-0.78 for patients <65 years of age and RR, 0.36; 95% CI, 0.18-0.72] for those ≥65 years). This was also true for antibiotics (RR, 0.41; 95% CI, 0.22-0.79 with vancomycin and RR, 0.09; 95% CI, 0.01-0.63 with fidaxomicin).

Safety

For safety, the majority of adverse events reported were mild to moderate in nature, mainly gastrointestinal issues, with similar prevalence between the SER-109 and placebo cohorts. In addition, SER-109 dose species were detected by week 1 and were associated with bile-acid profiles known to inhibit C difficile spore germination. However, there were no serious adverse events reported.

Three deaths did occur in the SER-109 group, but the investigators discovered the deaths were not related to the drug treatment.

“In patients with symptom resolution of C. difficile infection after treatment with standard-of-care antibiotics, oral administration of SER-109 was superior to placebo in reducing the risk of recurrent infection,” the authors wrote. “The observed safety profile of SER-109 was similar to that of placebo.”

The study, “SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection,” was published online in the New England Journal of Medicine.