An investigational therapy developed from healthy donor stool specimens treated with ethanol to eliminate pathogensâ€”the resulting spores of which are fractionated and encapsulated for oral delivery as SER-109â€”appears to effectively treat recurrent Clostridium difficile infection.
An investigational therapy developed from healthy donor stool specimens treated with ethanol to eliminate pathogens—the resulting spores of which are fractionated and encapsulated for oral delivery as SER-109—appears to effectively treat recurrent Clostridium difficile infection (CDI). Published ahead of print on February 8, 2016 in The Journal of Infectious Diseases, the phase 1b/2 trial found that treatment with the preparation not only successfully prevented recurrence of CDI in patients with a history of multiple recurrent disease, but also restored participants’ gut microbiome to a state similar to that of people without CDI.
Although fecal microbiota transplants (FMT) have been used successfully to reduce recurrence rates in patients with multiple CDI recurrences who have not responded to standard antibiotic treatment by improving the health of their microbiomes, FMT is not FDA-approved and requires informed consent from patients. On the other hand, the novel SER-109 is being developed under strict manufacturing and regulatory standards set by the FDA.
“This oral microbial preparation that contains a small fraction of the total microbiome works as well as, if not better than, FMT,” said senior author Elizabeth Hohmann, MD, chair and physician director of the Partners Human Research Committees in the Infectious Diseases Division at Massachusetts General Hospital. “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.”
The study results offer hope to the patients and providers affected by the 450,000 CDIs and 29,000 related mortalities in the United States each year, particularly the 25% to 30% of patients who relapse after treatment of the primary infection.
For these patients, the risk of failure only increases with each recurrence, from 40% with more than one recurrent to 60% with more than two. These failures occur because conventional therapy with antibiotics does not address the underlying gastrointestinal dysbiosis. Antibiotics also kill beneficial bacterial species in the gastrointestinal tract that normally keep potential pathogens at bay.
The current study comes on the heels of two Massachusetts general Hospital studies that showed in 2014 that the use of frozen fecal material from healthy, prescreened donors could be as effective as fresh material and that acid-resistant oral capsules to deliver FMT were nearly as effective as delivery via colonoscopy or nasogastric tube.
For the first stage of the study, 15 adult patients with three or more confirmed cases of CDI within the previous year received a 15 SER-109 capsules on each of two consecutive days. When the researchers found this treatment to be promising, a second group of 15 patients received doses that were 20 times lower and delivered in fewer capsules in single day.
Overall, 26 patients had no recurrence of CDI-positive diarrhea within the following 8 weeks. Although four patients experienced a return of diarrheal symptoms with CDI detectable in their stool after taking SER-109, symptoms were temporary in three patients, who did not require additional antibiotic treatment and were free of CDI at the end of 8 weeks. The fourth patient left the study. Thus, 96.7% of patients in the study achieved clinical resolution of their infection. When the study investigators tested participants’ microbial populations at the end of the 8 weeks, species contained in the SER-109 capsule were found to be established, as were other beneficial species not found in the novel product.