Seres Releases Positive Phase 3 Results of SER-109 for Recurrent C. Difficile Infection
In ECOSPOR III, the lead therapeutic candidate incorporated itself durably and rapidly into the microbiome to prevent recurrence, the company says.
Seres Therapeutics announced the presentation of data from its phase 3 ECOSPOR III study that suggested investigational microbiome-based therapeutic SER-109 prevents recurrent Clostridioides difficile infections (rCDI).
SER-109 prevents infection by rapidly establishing a long-lasting colony of beneficial gut microbes, which can help produce fatty acids that disrupt the C. difficile lifecycle, according to data presented at the 2022 Digestive Disease Week Annual Meeting.
“These results suggest that our investigational microbiome therapeutic, SER-109, is a potentially fast-acting intervention that can provide durable relief from rCDI when administered to vulnerable patients,” Matthew Henn, PhD, chief scientific officer at Seres, said in a statement. “Confirming the multiple mechanisms that bacteria in SER-109 utilize to prevent this notoriously challenging infection on the cellular and molecular level not only increases our confidence in this particular therapeutic, but it has the potential to help guide the design of the next generation of microbiome-based therapeutics.”
The data were shared as an oral presentation and poster at the meeting.
The ECOSPOR III study included 182 individuals with rCDI and was a multicenter, placebo-controlled, and randomized clinical trial. The trial previously demonstrated that SER-109 prevented rCDI in approximately 88% of individuals treated with the drug at the 8-week primary endpoint compared with approximately 60% of those in the placebo arm.
The safety was similar across both groups.
Additionally, a pre-planned exploratory analysis from the trial showed that approximately two-thirds of C. difficile infection recurrences occurred within the first 2 weeks following the antibiotic treatment when the microbiome is further decimated and the infection spores are free to germinate toxin-producing vegetative bacteria.
“These findings suggest that the first 2 weeks following antibiotic treatment is the time when microbiome therapeutics have the greatest potential benefit, by restoring bacterial diversity and disrupting the cycle of recurrent C. difficile,” Lisa von Moltke, MD, chief medical officer at Seres, said in the statement.
SER-109 introduces bacterial species into the gut in the form of spores, which germinate and incorporate into the microbiome and show up in stool as vegetative bacteria, in a process called engraftment.
Within a week of the treatment, the number of new bacterial species in the stool increased and remained higher than those in the placebo group for the entire 24-week study period. In the placebo group, bacterial diversity rebounded more slowly and to a lesser degree.
The pattern of the result was similar, regardless of which antibiotic individuals received, including fidaxomicin or vancomycin.
In the poster presentation, investigators preformed a post-hoc analysis to better understand how SER-109 prevents rCDI on a molecular level.
Investigators collected stool samples from individuals involved in the ECOSPOR III trial and analyzed the samples for changes in microbial makeup and fatty acid concentrations across the 8-weeks following treatment.
Individuals who received SER-109 had butyrate, hexanoate, and valerate levels that rapidly increased, starting within the 2-week window of vulnerability and remained higher than the placebo group.
These fatty acids have been shown to inhibit the grow of C. difficile.
In those who were in the placebo group and experienced rCDI, valerate levels tended to be lower compared with members of the placebo group who did not experience rCDI.
Seres expects to finalize a biologics license application submission for the drug with the FDA in mid-2022, which would make SER-109 potentially the first FDA-approved microbiome-based therapeutic for rCDI.
Seres Therapeutics presents phase Ill results of SER-109 for recurrent C. difficile infection at the Digestive Disease Week (DDW) Annual Meeting. BusinessWire. News release. May 22, 2022. Accessed May 23, 2022. https://www.businesswire.com/news/home/20220522005035/en