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Seres’ Microbiome Drug Fails to Reduce C. difficile Recurrence Risk
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Seres Therapeutics’ announced interim results from the phase 2 ECOSPOR trial of its investigational oral microbiome-based therapeutic SER-109, which failed to meet the primary endpoint of reducing the relative risk for recurrent Clostridium difficile infection at up to 8 weeks.
SER-109 (Seres Therapeutics) is an oral capsule prepared from healthy donor stool containing the dormant spores of about 50 species of Firmicutes, which are activated in the lower GI tract. It received orphan drug and breakthrough therapy designations from the FDA in 2015, and appeared to safely and effectively prevent C. difficile infection (CDI) recurrence in a previous phase 1b trial, with 86.7% of patients achieving the primary endpoint.
“These are unexpected clinical results in view of the positive data in our prior investigator-sponsored phase 1b trial, as well as in a wide range of supporting clinical and preclinical data,” Roger Pomerantz, MD, president, CEO and chairman of Seres, said in a press release. “Specifically, the recurrence rates observed in the overall SER-109 treatment group, in the age stratified subgroups, and in the placebo groups are inconsistent with our expectations.” The company will compare data from this and the previous trial of SER-109, and will communicate with the FDA to make necessary changes to the development program, he added.
In the current 24-week study performed at 36 centers in the U.S., researchers randomly assigned 89 patients who experienced at least three recurrent CDIs to a single dose of SER-109 (n = 59) containing 1x108 bacterial spores, or placebo (n = 30) after antibiotic treatment. Interim results show that CDI recurrence — defined as diarrhea for at least 2 consecutive days, a positive CDI test and need for antibiotics — occurred in 44% of the treatment group vs. 53% of controls. The relative risk for recurrence in the treatment vs. placebo groups was not statistically significant.
Moreover, among those aged younger than 65 years, 43% in the treatment group vs. 27% in the placebo group experienced recurrent infection, and among those aged older than 65 years, 45% vs. 80% experienced recurrence.
No differences in frequency or type of adverse events were observed between groups. The most common adverse events in both arms were gastrointestinal, the most common in the treatment arm were diarrhea, abdominal pain and flatulence, and no drug-related serious adverse events were reported.
“C. difficile infection treatment options, including unregulated fecal microbial transplants, remain poor,” Pomerantz said in the press release. “The confounding placebo data obtained in this study further highlight the significant need for new, effective, FDA regulated therapeutic options for these patients. We will take our learnings from this study and continue in our pioneering efforts to develop meaningful new microbiome therapeutics for C. difficile infection and other serious diseases.”
Disclosures: Pomerantz is employed by Seres Therapeutics.