SER-109 Results in Increase in Microbe-Producing Metabolites

May 23, 2022
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.

The live microbiota therapeutic has shown promise in treating patients with recurrent CDI.

New data on SER-109 presented during 2022 Digestive Disease Week Annual Meeting in San Diego shows the live microbiota therapeutic results in restoring microbe-associated metabolites known to prevent recurrent Clostridioides difficile infections (CDI).

A team, led by Kevin D. Litcofsky, MD, Seres Therapeutics, investigators changes in short, medium, and branched-chain fatty acids based on emerging studies regarding the potential role of microbe-associated metabolites in inhibiting C difficile growth and restoring gut homeostasis.

SER-109

Recent studies, including a phase 3 trial, have shown that SER-109, an oral investigational microbiome therapeutic made of purified Firmicutes spores, shown promise compared to placebo in reducing the risk of recurrent CDI at week 8.

In the phase 3 trial, the primary endpoint of reducing the risk was superior for patients treated SER-109 compared to placebo (12.4% vs. 39.8%, respectively; RR, 0.32; 95% CI, 0.18-0.58; P <0.001).

SER-109 also led to a higher engraftment of dose species and rapid conversion of primary to secondary bile acids, known inhibitors of C difficile spore germination and vegetative growth at weeks 1, 2, and 8.

The Study

In the study, the investigators examined patients with a history of at least 3 episodes of rCDI. Each patient was randomly assigned to be treated with either placebo or SER-109 following 10-21 days of standard of care antibiotic treatment.

The investigators also looked at a post-hoc analysis in which concentrations of short (acetate, propionate, butyrate), medium (valerate, hexanoate), and branched-chain (2-methylbutyrate, isobutyrate, isovalerate) fatty acids in subjects’ stool samples were measured from baseline to 1, 2, and 8 weeks post-treatment. The measurements were made by targeted liquid chromatography with tandem mass spectrometry.

The team also used two-sided Mann-Whitney U tests to determine statistical significance for metabolite comparisons between the different arms of the trial.

The baseline concentrations of all measured fatty acids were comparable between participants treated with SER-109 and placebo.

Fatty Acids

The concentrations of butyrate, a short-chain fatty acid, and valerate and hexanoate, medium-chain fatty acids, rapidly and significantly increased in patients treated with SER-109 compared to placebo.

The concentrations of microbe-produced metabolites also remained significantly higher in patients treated with SER-109 at week 2 and week 8 compared to placebo. The changes correlated with a greater magnitude of engraftment of SER-109 dose species through week 8 compared to placebo. However, other short and branched-chain fatty acids did not show consistent treatment related differences across the different time points.

The results show SER-109 could modulate multiple pathways critical to the rapid interruption of the C difficile life cycle.

“Compared to placebo, SER-109 demonstrated a rapid and sustained increase in the concentrations of butyrate, valerate, and hexanoate in parallel with SER-109 engraftment at weeks 1, 2 and 8 in subjects with a history of rCDI,” the authors wrote. “The increase in these microbe-produced metabolites was associated with a reduction in rCDI events suggesting that increasing fatty acid production may improve clinical outcomes.”

The study, “IMPACT OF SER-109, AN INVESTIGATIONAL MICROBIOME THERAPEUTIC, ON STOOL FATTY ACID METABOLITES IN A PHASE 3 RANDOMIZED TRIAL (ECOSPOR III) FOR TREATMENT OF RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION (CDI),” was published online by DDW 2022.


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