Analyzing Microbiome Diversity and Secondary Bile Acid Synthesis Following SER-109 Administration

True understanding of how the microbiome of the gut and its effects on various disease states is still largely not understood and that includes microbiota changes after administration of antimicrobial therapies and modalities.

For patients who suffer from health care-associated infections including recurrent Clostridioides difficile infection (rCDI), the traditional first-line of therapy is antibiotics, which is also the cause of the condition in the first place. Treatment options for recurrence for the condition have seen some changes in the last year.

Treatment for a first recurrence or multiply recurrent CDI (mrCDI) episodes are complex and may include antibiotics, monoclonal antibodies, or live biotherapeutic products. The FDA approved 2 live biotherapeutic products last year and are indicated for patients dealing with rCDI.

Investigators who presented data at the recent IDWeek on this subject pointed out that a better understanding of rCDI pathogenesis can help guide treatment. They reported microbiome findings of patients (pts) with frCDI and mrCDI from a post hoc analysis of 2 phase 3 trials with fecal microbiota spores, live-brpk (FMS; formerly SER-109 [Vowst]) manufactured an FDA-approved, microbiota-based therapeutic comprised of Firmicutes spores.

Seres developed Vowst, its oral microbiota treatment to prevent recurrent Clostridioides difficile infection (rCDI) and it is indicated to prevent rCDI in adults following antibacterial treatment and is commercialized by Nestlé Health Science in collaboration with Seres.

Investigators collected stool samples of patients with multiple rCDI in the Seres ECOSPOR 3 (n=158) and with a first recurrence of CDI or multiple CDI episodes in the ECOSPOR 4 (n=218) study at baseline (pre-dose) and week 1 post treatment. According to the investigators, a Shannon diversity was calculated from species profiles from analysis of whole metagenomic sequencing data using MetaPhlAn2. Primary (1°BA) and secondary bile acid (2°BA) concentrations were measured via targeted liquid chromatography–mass spectrometry panel. Subgroup differences were analyzed with linear mixed models.

“After antibiotics, patients with frCDI or mrCDI had low Shannon diversity and 2°BA concentrations that were no different between subgroups, highlighting a need for microbiome restoration,” the investigators wrote. “Both subgroups showed rapid, significant improvement in Shannon diversity and 2°BA concentrations and reductions in 1°BA after FMS, with comparable clinical outcomes.”

The company reported results recently of its quarterly report. Seres reported financial results for the third quarter which ended September 30, and within the earnings report they included Vowst which had a net sales of $7.6 million.

"With a broad label and compelling clinical profile, the launch of Vowst is off to a great start, exceeding our sales expectations," Seres President and CEO Eric Shaff, said in a statement associated with the quarterly report. "Performance metrics from this first full quarter of launch support our belief that the product is on track to deeply penetrate the rCDI market and fundamentally transform how this disease is managed.”

In terms of the outcome of the study reported at IDWeek, the investigators saw value in the newer C diff treatment for recurrence treatment and microbiome repair. “Both subgroups showed rapid, significant improvement in Shannon diversity and 2°BA concentrations and reductions in 1°BA after FMS, with comparable clinical outcomes. These data suggest that regardless of number of prior CDI episodes, FMS therapy following antibiotics may be an optimal treatment," they concluded.

Reference
Kelly C, Kraft C, et al. Analysis of Microbiome Diversity and Secondary Bile Acid Synthesis Following SER-109 or Placebo in Patients with First Recurrent or Multiply Recurrent Clostridioides difficile Infection. Presented at: IDWeek 2023. October 11-14, 2023; Boston, MA. Poster 655