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SER-109 engraftment was durable through week 24 and significantly higher than placebo at all time points for all comparisons.
New findings from the ECOSPOR III trial suggest SER-109 was superior to placebo at reducing the recurrence of clostridioides difficile infection (CDI) at week 8 and the engraftment of SER-109 was found durable through week 24 of the trial.
Moreover, the use of SER-109 additionally was associated with an absolute reduction in CDI recurrence rates sustained through week 24.
“These data support a two-pronged approach for the treatment of rCDI with standard-of-care antibiotics to kill vegetative C. difficile bacteria followed by investigational agent SER-109 to durably repair the disrupted microbiome through engraftment of Firmicutes bacteria,” wrote study author Matthew Henn, PhD, Chief Scientific Officer, Seres.
These data were presented at the 2022 Digestive Disease Week Annual Meeting in San Diego, California.
In the double-blind, randomized ECOSPOR III trial, SER-109 met the primary endpoint and was found superior to placebo (12.4% vs 39.8%; RR, 0.32; 95% CI, 0.18 - 0.58; P <.001). Additionally, clinical response was associated with SER-109 species engraftment, while rapid engraftment at week 1 was associated with conversion of primary to secondary bile acids, which may inhibit the life cycle of C difficile.
However, investigators noted the durability of microbiome therapeutics is unknown. Thus, a total of 182 toxin+ adult subjects with symptom resolution following antibiotics for 10 - 21 days were randomized to SER-109 or placebo in a 1:1 ratio.
The investigators defined CDI recurrence as ≥3 uniformed stools/day for ≥48 hours, C. difficile stool toxin test, and investigator decision to treat. The clinical endpoints included reduction of recurrence at week 8 (primary endpoint) and through week 24 (secondary endpoint).
For the pre-planned exploratory analysis, the durability of engraftment was assessed as the number of newly appearing SER-109 species observed post-dosing through week 24, but not present at baseline in subject stool samples. Moreover, metagenomic sequencing in conjunction with Metaphlan microbiome composition profiling tool identified bacterial species. The investigators used two-sided Mann-Whitney U tests to determine statistical significance between SER-109 and placebo arms.
The stool samples at week 24 were available from 53 subjects in the SER-109 arm compared to 44 subjects in the placebo arm. Investigators noted the main reason for loss of subjects was CDI recurrence, including 19 recurrences in the SER-109 arm compared to 44 recurrences in the placebo arm.
Data show engraftment in the SER-109 arm is rapid and durably maintained above levels observed in placebo out to week 24 (P <.001 for all comparisons). These observations were associated with reduction of absolute risk of recurrent CDI through all time points measured (22.1% at week 4, 27.4% at week 8, 28.3% at week 12, and 26.0% at week 24).
Within the fidaxomicin subgroup, high recurrence rates in the placebo arm compared with SER-109 (45.8% vs 4% recurrence by 8 weeks) suggest that this subgroup benefit from SER-109 treatment.
Moreover, investigators found greater numbers of SER-109 dose species through week 24 in both the vancomycin and fidaxomicin subpopulations that received SER-109, helping suggest that SER-109 durably engrafts regardless of antibiotic pretreatment.
The study, “Engraftment of Investigational Microiome Therapeutic SER-109 Is Durable Through 24 Weeks in a Randomized Trial (ECOSPOR III) For the Treatment of Recurrent Clostridioides Difficile Infection,” was presented at DDW 2022.