Drug/Device Pipeline

Microbiome Therapy Shows Benefit in Ulcerative Colitis

Stephen B. Hanauer, MD
Stephen B. Hanauer

SER-287, an oral microbiome treatment in development for inflammatory bowel disease, showed positive results in patients with ulcerative colitis in a phase 1b clinical study, Seres Therapeutics announced.

The results showed benefit in clinical remission rates, improved mucosal appearance on endoscopy, and no significant safety issues, according to a press release. The company said it now plans to rapidly advance the treatment’s development in ulcerative colitis.

The therapy consists of biologically sourced live bacterial spores, and is thought to work by altering microbiome dysbiosis to reduce inflammation without immunosuppression.

“New treatment modalities are urgently needed that both address the inadequate levels of remission with available ulcerative colitis therapies, and have a favorable safety profile,” Stephen B. Hanauer, MD, professor of medicine in the division of gastroenterology and hepatology at Feinberg School of Medicine, Northwestern University in Chicago, said in the press release. “The dose dependent and highly positive clinical remission rates and endoscopic scores from this study are very encouraging. SER-287 may represent an important new treatment option for patients.”

In this double-blind induction study, researchers enrolled 58 patients with mild-to-moderate UC from 20 U.S. sites, and randomly assigned them to receive one of three SER-287 regimens or placebo for 8 weeks. Treatment arms included daily dosing with vancomycin pre-treatment, and weekly dosing with and without vancomycin pre-treatment.

Safety, tolerability and change in microbiome through 8 weeks served as the co-primary endpoints. The company said the safety and tolerability profile was “very favorable,” as treatment and placebo groups showed similar adverse events, and no serious adverse events related to the study drug occurred.

Data on the microbiome endpoint are expected in the coming months, including an analysis of any differences in response across the three drug product lots used in the study, which were based on three separate individuals’ donor material.

Secondary efficacy endpoints included clinical remission rates, endoscopic improvement and clinical response, as recommended by the FDA, which were assessed by a central reader.

Results based on intent to treat “observed case” data on 53 patients showed a dose-dependent improvement in clinical remission rates and endoscopic scores at 8 weeks, with the most significant effects appearing to occur in the daily dose arm (40% vs. 10% with placebo for both endpoints). Vancomycin did not clearly change the regimens’ efficacy.

The company said in plans to present additional results at an upcoming scientific meeting.

“The clinical data demonstrate the potential for microbiome therapeutics to provide an effective and safer alternative treatment modality for patients suffering from ulcerative colitis,” Roger J. Pomerantz, MD, president, CEO and chairman of Seres, said in the press release. “Based on the strength of these data, Seres intends to work expeditiously to advance SER-287 into more advanced development studies. 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.”

The press release noted the company’s IBD pipeline also includes SER-301, “a therapeutic candidate comprised of a consortium of rationally selected, fermented bacterial species. The pending SER-287 microbiome data will be used to inform the final composition of SER-301, as the company plans a SER-301 investigational new drug (IND) application.”

Disclosures: Pomerantz is employed by Seres, and Hanauer reports he is a scientific advisor for Seres.

Stephen B. Hanauer, MD
Stephen B. Hanauer

SER-287, an oral microbiome treatment in development for inflammatory bowel disease, showed positive results in patients with ulcerative colitis in a phase 1b clinical study, Seres Therapeutics announced.

The results showed benefit in clinical remission rates, improved mucosal appearance on endoscopy, and no significant safety issues, according to a press release. The company said it now plans to rapidly advance the treatment’s development in ulcerative colitis.

The therapy consists of biologically sourced live bacterial spores, and is thought to work by altering microbiome dysbiosis to reduce inflammation without immunosuppression.

“New treatment modalities are urgently needed that both address the inadequate levels of remission with available ulcerative colitis therapies, and have a favorable safety profile,” Stephen B. Hanauer, MD, professor of medicine in the division of gastroenterology and hepatology at Feinberg School of Medicine, Northwestern University in Chicago, said in the press release. “The dose dependent and highly positive clinical remission rates and endoscopic scores from this study are very encouraging. SER-287 may represent an important new treatment option for patients.”

In this double-blind induction study, researchers enrolled 58 patients with mild-to-moderate UC from 20 U.S. sites, and randomly assigned them to receive one of three SER-287 regimens or placebo for 8 weeks. Treatment arms included daily dosing with vancomycin pre-treatment, and weekly dosing with and without vancomycin pre-treatment.

Safety, tolerability and change in microbiome through 8 weeks served as the co-primary endpoints. The company said the safety and tolerability profile was “very favorable,” as treatment and placebo groups showed similar adverse events, and no serious adverse events related to the study drug occurred.

Data on the microbiome endpoint are expected in the coming months, including an analysis of any differences in response across the three drug product lots used in the study, which were based on three separate individuals’ donor material.

Secondary efficacy endpoints included clinical remission rates, endoscopic improvement and clinical response, as recommended by the FDA, which were assessed by a central reader.

Results based on intent to treat “observed case” data on 53 patients showed a dose-dependent improvement in clinical remission rates and endoscopic scores at 8 weeks, with the most significant effects appearing to occur in the daily dose arm (40% vs. 10% with placebo for both endpoints). Vancomycin did not clearly change the regimens’ efficacy.

The company said in plans to present additional results at an upcoming scientific meeting.

“The clinical data demonstrate the potential for microbiome therapeutics to provide an effective and safer alternative treatment modality for patients suffering from ulcerative colitis,” Roger J. Pomerantz, MD, president, CEO and chairman of Seres, said in the press release. “Based on the strength of these data, Seres intends to work expeditiously to advance SER-287 into more advanced development studies. 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.”

The press release noted the company’s IBD pipeline also includes SER-301, “a therapeutic candidate comprised of a consortium of rationally selected, fermented bacterial species. The pending SER-287 microbiome data will be used to inform the final composition of SER-301, as the company plans a SER-301 investigational new drug (IND) application.”

Disclosures: Pomerantz is employed by Seres, and Hanauer reports he is a scientific advisor for Seres.

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