The evolving research on the gut and the connections with the microbiome has been evolving. Researchers have been gleaning data from smaller studies to capture a glimpse of the bigger picture of the microbiome as it relates to health care associated infections (HAI). One area of ongoing study has been the review of the microbiome around patients with recurrent Clostridioides difficile infection (rCDI).
During IDWeek, a study was presented looking at patients’ microbiome profiles to determine if there were differences at the start of trials based on their diagnostic testing and whether the microbiome recovery differed between subgroups after receiving the oral microbiota treatment Vowst (SER-109) for rCDI.
Back in April, the FDA approved Vowst to prevent rCDI. Biologics License Acceptance came on SER-109’s Prescription Drug User Fee Act (PDUFA) action date. With the decision, SER-109 became the first-ever FDA-approved oral microbiome therapeutic.
SER-109 was developed by the biotechnology company Seres Therapeutics, and the therapy works to restore the gut by competing metabolically with C diff and restoring colonization resistance.
What You Should Know
The study analyzed patients from two phase 3 trials, ECOSPOR 3 and ECOSPOR 4, with varying diagnostic testing methods for rCDI. It found that the administration of fecal microbiota spores, live-brpk (formerly SER-109), was associated with a low rCDI recurrence rate within eight weeks.
Regardless of the diagnostic method used, the study found that the gut microbiome profiles of rCDI patients underwent rapid changes after treatment with fecal microbiota spores (FMS).
Vowst works by restoring the gut's microbiome, competing metabolically with C diff, and enhancing colonization resistance.
Study Methodology and Results
Pretreatment stool samples were obtained from patients in theECOSPOR 3 trial, a placebo-controlled study in patients with ≥2 prior rCDI episodes and diagnosis by toxin EIA (TOX+) and b) ECOSPOR 4, an open-label trial in pts with ≥1 prior rCDI and diagnosis by TOX+ with/without PCR or PCR+, according to the investigators.1
“In 2 phase 3 trials with varied diagnostic testing methods, dosing with fecal microbiota spores, live-brpk (FMS; formerly SER-109) was associated with low rCDI rate ≤8 wks (ECOSPOR III: FMS, 12% vs placebo, 40%; ECOSPOR IV: FMS, 9%),” the investigators wrote. “In ECOSPOR IV, recurrence rates with FMS ≤8 wks were similar by diagnostic method (10.4% [95% CI, 6.5%–15.6%] in patients [pts] toxin-positive by EIA with/without PCR vs 4.3% [95% CI, 0.9%–12.2%] in pts with toxin gene detection by PCR only [PCR+]).”1
Investigators conducted a post hoc analysis and among the 349 patients who received Vowst in the analysis, 69 (19.8%) were diagnosed by PCR alone and 276 (79.1%) were diagnosed with a toxin test with or without PCR.1
“Baseline Shannon diversity was similarly low across TOX+ and PCR+ subgroups (P>0.05); engraftment magnitude after FMS was comparable across trials (P>0.05). Baseline 1°BA concentrations were comparable across trials (P>0.05) and subgroups (P>0.05) and decreased by Week 1 after FMS in TOX+ (P< 0.001) and PCR+ (P< 0.001) subgroups,” the investigators wrote.
“The data we are presenting this year at IDWeek build upon our earlier findings that the gastrointestinal microbiome is similarly disrupted in patients with first or multiple rCDI. The introduction of Vowst has provided a means to alleviate suffering and health risks associated with recurrent instances of this serious disease," said Matthew Henn, PhD, chief scientific officer at Seres in a statement.2
“Regardless of diagnostic method, microbiota diversity appeared similarly disrupted at baseline and improved rapidly by 1 week after fecal microbiota spores (FMS),” the investigators concluded.
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1. Gonzales-Lunas A, Litcofsky K, et al. Rapid Change in Microbiome Profiles Regardless of Diagnostic Method in a Post Hoc Comparative Analysis of Phase 3 Trials of Fecal Microbiota Spores, Live-brpk (formerly SER-109) for the Prevention of Recurrent Clostridioides difficile Infection (rCDI). Presented at: IDWeek 2023. October 11-14, 2023; Boston, MA. Abstract 653.
2. Seres Therapeutics to Highlight Vowst Data at IDWeek. Seres Therapeutics. October 12, 2023. Accessed October 19, 2023. https://ir.serestherapeutics.com/news-releases/news-release-details/seres-therapeutics-highlight-vowsttm-data-idweek