Firmicutes bacteria can help produce metabolites that maintain intestinal barriers and mucosal immunity.
A new drug targeting gut microbiota could help patients with ulcerative colitis achieve a faster clinical remission.
A team, led by Matthew R. Henn, Seres Therapeutics, evaluated the safety and efficacy of SER-287, an oral formulation of Firmicutes spores, as well as the effects of vancomycin preconditioning on the expansion or engraftment of SER-287 species in the colon, in patients with ulcerative colitis.
Firmicutes bacteria produce metabolites that maintain the intestinal barrier and provide mucosal immunity. Firmicutes are reduced in the intestinal microbiota of patients suffering from ulcerative colitis.
In the double blind phase 1b trial, the investigators examined 58 adults with active mild-to-moderate ulcerative colitis, defined as a modified Mayo score 4-10 and endoscopic subscores of at least 1.
Each patient received 6 days of preconditioning with oral vancomycin 125 mg 4 times daily or placebo. This was followed by either placebo or SER-287 once weekly or vancomycin followed by SER-287 once weekly or SER-287 once daily. Each patient was randomized in a 2:3:3:3 ratio to the 4 groups.
The investigators sought clinical endpoints of safety and clinical remission, defined as modified Mayo score ≤ 2 and endoscopic subscores 0 or 1. They also pursued microbiome endpoints including SER-287 engraftment (dose species detected in stool after, but not before, SER-287 administration).
The team measured the engraftment of SER-287 and changes in microbiome composition and associated metabolites by analyses of stool specimens collected at baseline, after preconditioning, and during and 4 weeks after administration of the study drug or placebo.
The proportions of patients with adverse events ultimately did not differ significantly among the different treatment groups.
However, there were a higher proportion of patients in the daily treatment groups of vancomycin/SER-287 (40%) that achieved clinical remission at week 8 than patients in the placebo/placebo group (0), placebo/SER-287 weekly group (13.3%), or vancomycin/SER-287 weekly group (17.7%) (P = 0.024 for vancomycin/SER-287 daily vs placebo/placebo).
By day 7, there were higher numbers of SER-287 dose species detected in stool samples from all of the SER-287 groups compared with the placebo group (P <0.05). However, this difference was not maintained beyond day 7 in the placebo/SER-287 weekly group.
In the vancomycin groups, there was a greater number of dose species detected in stool collected on day 10, as well as all subsequent time points, through 4 weeks post-dosing, compared with the placebo group (P <0.05).
Changes in fecal microbiome composition and metabolites were associated with both vancomycin/SER-287 groups.
“In this small phase 1b trial of limited duration, the safety and tolerability of SER-287 were similar to placebo,” the authors wrote. “SER-287 following vancomycin was significantly more effective than placebo for induction of remission in patients with active mild-to-moderate UC. Engraftment of dose species was facilitated by vancomycin preconditioning and daily dosing of SER-287.”
The study, “A Phase 1b safety study of SER-287, a spore-based microbiome therapeutic, for active mild to moderate ulcerative colitis,” was published online in Gastroenterology.