Seres plots ulcerative colitis trial drive after posting 1b data

Seres Therapeutics has posted top-line data from a phase 1b of SER-287 in ulcerative colitis. The microbiome pioneer thinks the data support the rapid advance of SER-287 deeper into the clinic, although question marks about the results mean that doubts remain.

Investigators enrolled 58 patients with mild-to-moderate ulcerative colitis whose condition had not been brought under control by existing nonbiologic therapies. The patients were split up into four arms. About half of the subjects were pretreated with the antibiotic vancomycin and then given either daily or weekly doses of SER-287 for eight weeks. The rest received placebo pretreatment followed by either weekly doses of SER-287 or daily placebos.

Seres focused its release detailing the top-line data on clinical remission. Six of the 15 patients who received vancomycin followed by daily doses of SER-287 went into remission, as compared to one of the 10 who only received placebo. The remission rate fell sharply when SER-287 was given weekly, regardless of whether the patients were pretreated with vancomycin.

The data have emboldened Seres to plan a broad push deeper into development.

“We plan to further evaluate SER-287 in mild, moderate and severe forms of ulcerative colitis, in maintenance after induction therapy, and we also intend to assess development in Crohn’s disease, and pediatric forms of inflammatory bowel disease. We expect to discuss these data with the FDA as soon as possible, to determine the most accelerated path to advance SER-287 development,” Seres CEO Roger Pomerantz, M.D., said in a statement. 

Seres is embarking on that clinical trial push despite the data leaving scope for doubt about the effect of SER-287. The clinical response rate in the placebo-placebo cohort matched or beat those from the three SER-287 arms. And the 40% clinical remission rate from the best-performing cohort merely puts SER-287 in the same ballpark as existing drugs such as Takeda’s Entyvio. It doesn’t look like SER-287 will blow away the competition in terms of efficacy.

SER-287 could carve out a niche with competitive efficacy and improved safety, though and on this last point the trial is on firmer ground. Seres called the tolerability profile seen in the clinical trial “very favorable,” adding that no serious adverse events were linked to SER-287.

Safety was one of two coprimary endpoints. Seres has yet to release data against the second main endpoint, which looked at changes to the intestinal microbiome of patients following treatment.

Seres thinks changing the gut microbiome will improve outcomes, a hypothesis backed up by success stories from ulcerative colitis patients who have received fecal transplants. Those cases go some way to derisking the program, although it is unclear whether SER-287 can be as effective as fecal transplants.

Future clinical trials will answer that question more definitively but for now skeptics about the likelihood of Seres’ approach working have ample ammunition.