Seres Therapeutics ($MCRB) has suffered a sizable setback to its microbiome R&D ambitions. In a Phase II trial, the oral microbiome therapeutic SER-109 failed to outperform a placebo in terms of cutting the risk of Clostridium difficile infection (CDI), leaving the biotech scraping through the results in search a path forward for the program.
The Phase II study enrolled 89 subjects and randomized them to receive either SER-109 or a placebo. Once the subjects completed antibiotic treatment for CDI, two-thirds of them received a single oral dose of the bacterial spores that make up SER-109, with the remaining one-third getting a placebo. Seres had hoped SER-109 would recalibrate participants’ microbiomes, resulting in fewer subjects in the treatment arm experiencing recurrences of CDI.
Unfortunately for Seres, the 8-week data tell a different story. In the SER-109 arm of the study, 44% of participants experience a recurrence of CDI. A little more than half of subjects who received the placebo saw their CDI recur. When Seres crunched the numbers, this difference fell short of being a statistically significant reduction in relative risk of CDI recurrence, leaving the firm with a Phase II trial that failed to meet its primary endpoint. Among subjects aged under 65 years old, the placebo bested SER-109.
Seres was blindsided by multiple aspects of the data. “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,” CEO Roger Pomerantz said in a statement.
The next step for Seres is to compare the Phase II data to results generated in an earlier investigator sponsored Phase Ib trial. Once Seres has a handle on the situation, it plans to talk with FDA--which awarded SER-109 breakthrough status last year--and revise its development strategy as required.
Shares in Seres were down more than 70% in premarket trading.
The fallout from the setback could extend well beyond Seres, which has been held up as an example of the potential of the microbiome sector, both from a financial and therapeutic perspective. In the good times, such as after Seres pulled off a $134 million IPO, the company has delivered a sector-wide boost to the nascent field.
Speaking to FierceBiotech late last year, Isabelle de Cremoux, the CEO of Seventure Partners and its Novartis ($NVS)-backed microbiome fund, identified the Seres IPO as a tipping point for the sector.
“After Seres’ IPO, the VC community started to wake up and say, ‘oh, maybe there’s something in the microbiome field that we better watch,’” she said.
Now, the sector is facing its first major clinical-phase blowup. Once again, the microbiome field and those who invest in it are watching Seres closely.
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