FDA clears new trial for failed C. difficile drug

Seres Therapeutics announced that after a positive Type B meeting with the FDA, it plans to initiate a new phase 2 clinical study of SER-109, a microbiome-based therapeutic for recurrent Clostridium difficile infection that failed in a previous trial.

“The FDA has agreed that this new trial may qualify as a pivotal study with achievement of a persuasive clinical effect and addressing FDA requirements, including clinical and statistical factors, an adequately sized safety database, and certain CMC parameters,” according to a press release from the company.

SER-109 (Seres Therapeutics) is an oral capsule prepared from healthy donor stool containing dormant Firmicute spores that are activated in the lower GI tract. It received orphan drug and breakthrough therapy designations from the FDA in 2015, and appeared to prevent CDI recurrence in a previous phase 1b trial, with 86.7% of patients achieving the primary endpoint. Last year, however, the drug unexpectedly failed to reduce the relative risk for recurrent CDI in the phase 2 ECOSPOR trial, which the company determined may have been influenced by misdiagnosis of recurrent CDI and suboptimal dosing in some trial participants.

Now, Seres and the FDA have agreed on a new phase 2 trial design (ECOSPOR 3), in which investigators will randomly assign about 320 patients with multiple recurrent CDI to receive either SER-109 or placebo. In this 24-week trial, recurrent CDI diagnosis for study entry and for endpoint analysis will be confirmed by C. difficile cytotoxin assay to ensure accurate CDI measurement. Moreover, patients in the treatment group will receive a 10 times higher dose of SER-109 than that given in the prior study. CDI recurrence rate at up to 8 weeks after dosing will serve as the primary endpoint.

“We are pleased to have received highly constructive guidance from the FDA regarding further SER-109 clinical development and we plan to initiate a new clinical study as soon as possible,” Roger J. Pomerantz, MD, President, CEO and Chairman of Seres, said in the press release. “Based on our learnings and dialogue with the FDA, we believe that we are now positioned to initiate a robust clinical study that may provide the basis for SER-109 approval. There is an urgent need for improved treatments for C. difficile infection, and we believe SER-109 has great potential to address the underlying cause of the disease and become the first approved microbiome therapeutic in this new field of medicine.” – by Adam Leitenberger

Disclosures: Pomerantz is employed by Seres Therapeutics.