SER-109 well tolerated, reduces recurrent C. difficile infection for 24 weeks

SER-109, an investigational treatment for the oral microbiome, was well tolerated and had sustained reductions in recurrence rates Clostridioides hard infection for 24 weeks, with benefits as early as week 2, according to the data.

SER-109 (Seres Therapeutics) is an oral capsule prepared from healthy donor stool containing dormant Firmicute spores that are activated in the lower gastrointestinal tract. It received orphan drug and breakthrough therapy designations from the FDA in 2015 and appears to prevent It’s hard recurrent infection (CDI) in a previous phase 1b trial, with 86.7% of patients reaching the primary endpoint.

In 2016, however, the drug unexpectedly failed to reduce the relative risk of recurrent CDI in a phase 2 trial, which the company says may have been influenced by misdiagnosis of recurrent CDI and suboptimal dosing in some trial participants. In 2017, the FDA cleared Seres to conduct a new phase 2 trial. They agreed on a new trial design, in which researchers randomly assigned patients with multiple recurrent CDIs to receive either SER-109, a placebo. The recurrent diagnosis of CDI was confirmed by It’s hard cytotoxin assay to ensure accurate measurement of CDI.

Earlier this year, data from a phase 3 trial that was published in The New England Journal of Medicine showed that SER-109 was superior to placebo in reducing the risk of recurrent CDI in patients with three or more episodes (12% versus 40%; RR=0.32; 95% CI, 0.18- 0.58).

The current analysis assessed pre-specified secondary endpoints of adverse events and durability of response over 24 weeks.

For the trial, Stuart H. Cohen, MD, chief of the division of infectious diseases and director of hospital epidemiology and infection control at the University of California Davis Health, and colleagues randomly assigned 182 patients with recurrent CDI (3 episodes of CDI in 12 months) to receive four capsules of SER-109 or a placebo daily for 3 days. Comorbidities were common among the patients, with an average Charlson Comorbidity Index score of 4.1 in the SER-109 group and 4.2 in the placebo group, the researchers said.

A significantly lower proportion of patients in the SER-109 group experienced recurrent CDI at weeks 4, 8, 12 and 24 compared to patients in the placebo group. Overall, 21.3% of patients in the SER-109 group had recurrent CDI during the study period versus 47.3% in the placebo group.

Of those who had recurrent CDI, 65.1% experienced a recurrence at week 4. Only 6.3% of patients had a recurrence between weeks 12 and 24.

In terms of tolerability, treatment-emergent adverse events that occurred in at least 5% of patients — and more frequently in the SER-109 group — included abdominal distension, constipation, diarrhea, and urinary tract infection, according to Cohen et al. these partner’work.

Fifteen patients in the SER-109 group and 19 in the placebo group experienced serious adverse events, none of which were considered drug-related, the researchers reported.

One patient in each group withdrew from the study due to treatment-related serious adverse events, and one patient in the SER-109 group and two in the placebo group discontinued the study “due to worsening pre-existing conditions,” Cohen and colleagues wrote. Three deaths occurred following the procedure, but none were drug-related.

“The benefit of SER-109 was evident as early as week 2, highlighting the need for rapid microbiome repair after completing standard antibiotics,” Cohen and colleagues wrote. “One of the limitations of the study was the exclusion of patients with a first recurrence, although this subgroup is also characterized by microbiome disruption. These data support a potential role for this therapeutic experimental oral microbiome in the treatment of patients with this debilitating infection.