SER-109, an oral microbiome therapeutic, safely protects against Clostridioides difficile recurrence for up to 24 weeks, according to a recent phase 3 trial. Three days of treatment with purified Firmicutes spores reduced risk of recurrence by 54%, suggesting a sustained, clinically meaningful response, according to a multicenter study presented at this year’s Digestive Disease Week® (DDW).
“Antibiotics targeted against C. difficile bacteria are necessary but insufficient to achieve a durable clinical response because they have no effect on C. difficile spores that germinate within a disrupted microbiome,” the investigators reported at the meeting.
“The manufacturing processes for SER-109 are designed to inactivate potential pathogens, while enriching for beneficial Firmicutes spores, which play a central role in inhibiting the cycle of C. difficile,” said Louis Y. Korman, MD, a gastroenterologist in Washington, who was lead author.
Extended data from ECOSPOR-III
The ECOSPOR-III trial involved 182 patients with at least three episodes of C. difficile infection in the previous 12 months. Patients underwent 10-21 days of antibiotic therapy with fidaxomicin or vancomycin to resolve symptoms before they were then randomized in a 1:1 ratio to receive either SER-109 (four capsules daily for 3 days) or placebo, with stratification by specific antibiotic and patient age (threshold of 65 years).
The primary objectives were safety and efficacy at 8 weeks. These results, which were previously reported at ACG 2020, showed a 68% relative risk reduction in the SER-109 group, and favorable safety data. The findings presented at DDW added to those earlier ones by providing safety and efficacy data extending to week 24. At this time point, patients treated with SER-109 had a 54% relative risk reduction in C. difficile recurrence. Recurrence rates were 21.3% and 47.3% for the treatment and placebo groups, respectively (P less than .001).
Patients 65 years and older benefited the most from SER-109 therapy, based on a relative risk reduction of 56% (P less than .001), versus a 49% relative risk reduction (lacking statistical significance) for patients younger than 65 years (P = .093). The specific antibiotic therapy patients received also appeared to impact outcomes. Patients treated with fidaxomicin had a 73% relative risk reduction (P = .009), compared with 48% for vancomycin (P = .006). Safety profiles were similar between study arms.
“By enriching for Firmicutes spores, SER-109 achieves high efficacy, while mitigating risk of transmitting infectious agents and represents a major paradigm shift in the clinical management of patients with recurrent C. difficile infection,” the investigators concluded, noting that “an open-label study for patients with recurrent C. difficile infection is currently enrolling.”
Microbiome restoration therapies
According to Sahil Khanna, MBBS, professor of medicine at Mayo Clinic, Rochester, Minn., these findings “advance the field” because they show a sustained response. “We know that microbiome restoration therapies help restore colonization resistance,” Dr. Khanna said in an interview, noting that they offer benefits comparable to fecal microbiota transplantation (FMT) without the downsides.
Dr. Sahil Khanna
“The trouble with FMT is that it’s heterogenous – everybody does it differently … and also it’s an invasive procedure,” Dr. Khanna said. He noted that FMT may transmit infectious agents between donors and patients, which isn’t an issue with purified products such as SER-109.
Several other standardized microbiota restoration products are under development, Dr. Khanna said, including an enema form (RBX2660) in phase 3 testing, and two other capsules (CP101 and VE303) in phase 2 trials. “The hope would be that one or more of these products would be approved for clinical use in the near future and would probably replace the vast majority of FMT [procedures] that we do clinically,” Dr. Khanna said. “That’s where the field is headed.”
The investigators reported no conflicts of interest. Dr. Khanna disclosed research support from Finch, Rebiotix/Ferring, Vedanta, and Seres.