Seres's SER-109 will miss the primary end point in its Phase II trial in patients with Clostridium difficile infection, showed an interim analysis of the trial last month. The setback highlights the uncertainty ahead for a burgeoning field of microbiome-based drugs.

Credit: NPG

Faecal microbiota transplantations are effective for the treatment of C. difficile infections, but they require the transfer of minimally processed and uncharacterized faecal matter from healthy donors to recipients (N. Engl. J. Med. 368, 407–415; 2013). By fractionating and processing the stool of healthy volunteers to purify for approximately 50 species of Firmicute spores, Seres hopes that its SER-109 will provide a safer, more palatable, alternative to faecal microbiota transplantation. Seres's orally delivered drug is the first-ever clinically studied synthetic microbiome therapeutic, and it received breakthrough therapy designation from the US FDA in 2015 after producing promising Phase I/II data (J. Infect Dis. 214, 173–181; 2016).

An interim analysis of the 89-subject Phase II trial of the drug recently found, however, that SER-109 is not on track to reduce the relative risk of recurrence of C. difficile infection at 8 weeks. Seres's CEO Roger Pomerantz noted that recurrence rates in both the treatment arm and the placebo arm were inconsistent with the company's expectations. Seres did not observe any difference in the adverse event frequency between treatment and placebo. The trial is ongoing, while Seres re-evaluates its development plan for SER-109.

Although there is great excitement over the role of the microbiome in health and disease, the disappointing results show how hard it will be to distil treatment strategies from complex bacterial imbalances.