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Novel microbiome therapy appears to prevent recurrent C. difficile infection
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An investigational oral microbiome-based therapeutic safely and effectively prevented recurrent Clostridium difficile infection in patients with multiple recurrent infections, according to results from a phase 1b/2 trial.
SER-109 (Seres Therapeutics) is an oral capsule prepared from healthy prescreened donor stool that contains the dormant spores of about 50 species of Firmicutes that become active in the lower GI tract.
“This oral microbial preparation that contains a small fraction of the total microbiome works as well as, if not better than, [fecal microbiota transplant],” Elizabeth Hohmann, MD, from the Massachusetts General Hospital Infectious Diseases Division, said in a press release. “These few key species seem to work in restoring a healthy microbiome, and other, beneficial species not in the capsules return, while harmful bacteria are removed. The product is also designed to be safer than FMT, by eliminating the potential for transmission of pathogens that might be present in donor fecal material.”
Elizabeth Hohmann
To assess SER-109’s safety, efficacy and engraftment, Hohmann and colleagues performed an open-label, single-arm, descending dose study involving 30 patients (median age, 66.5 years [range, 22-88 years]; 67% women) at four U.S. medical centers who had at least three confirmed CDI episodes in the past year. All patients had a clinical response to antibiotic therapy for the current CDI episode immediately before receiving SER-109.
Patients stopped taking antibiotics 2 days before treatment, and received a bowel preparation 1 day before treatment. Half of the patients received a higher dose of spores in 30 capsules taken over 2 days, and the other half received a lower dose of spores in 1 to 12 capsules in a single day.
Prevention of recurrent CDI during 8-weeks of follow-up served as the primary endpoint. Stool samples were also analyzed before and after treatment to determine the impact of treatment on the gut microbiota.
Overall, 86.7% of patients achieved the primary endpoint, and outcomes were comparable in both dose groups. Moreover, three patients who did not meet the primary endpoint had early, self-limiting C. difficile-positive diarrhea, did not require antibiotics and tested negative for C. difficile at week 8, resulting in a clinical resolution rate of 96.7%. The treatment was well tolerated, and treatment-related adverse events occurred in half of patients (all mild to moderate in severity), the most common of which were diarrhea, nausea and abdominal pain.
Diversity of gut microbiota increased significantly at 8 weeks (P < .01), and these changes were rapid and durable.
The research team concluded that these results “support further development of SER-109 as a novel biologic agent that restores the gut microbiome as a primary defense against potential pathogens, such as C. difficile.”
“This was a great collaboration between academic medical centers and a biopharma company that we hope will lead to an effective, easy-to-take treatment for C. difficile infection, which can be a serious, recurring problem,” Hohmann said in the press release. “We also hope there will be other applications for this novel ‘ecobiotic’ — a drug designed to restore a community of beneficial microbes.” – by Adam Leitenberger
Disclosure: This study was funded by Seres Therapeutics. Hohmann reports she was an investigator in the SER-001 trial. Please see the full study for a list of all other authors’ relevant financial disclosures.
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