The FDA approved the first fecal microbiota product (Vowst, Seres Therapeutics) that is taken orally to prevent recurrent Clostridioides difficile infection (rCDI) in people who are 18 years of age and older, following antibacterial treatment for rCDI.

“Today’s approval provides patients and healthcare providers a new way to help prevent recurrent C. difficile infection,” said Peter Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation and Research. “The availability of a fecal microbiota product that can be taken orally is a significant step forward in advancing patient care and accessibility for individuals who have experienced this disease that can be potentially life-threatening.”

The safety of fecal microbiota was evaluated in a randomized, double-blind, placebo-controlled clinical study and an open-label trial conducted in the United States and Canada. The participants had rCDI, were 48 to 96 hours post-antibacterial treatment and their symptoms were controlled. Across both studies, 346 individuals who were at least 18 years of age with rCDI received all scheduled doses of fecal microbiota. 

The effectiveness of fecal microbiota was evaluated in the randomized, placebo-controlled clinical study in which 89 participants received fecal microbiota and 93 received placebo. Through eight weeks after treatment, the rate of rCDI in fecal microbiota–treated patients was lower compared with the placebo-treated participants (12.4% vs. 39.8%).

Specifically, ECOSPOR III (ClinicalTrials.gov Identifier: NCT03183128) and ECOSPOR IV (ClinicalTrials.gov Identifier: NCT03183141) found:

ECOSPOR III (SERES-012): A multicenter, randomized, placebo-controlled study that enrolled 182 adults with rCDI showed that 88% of participants in the fecal microbiota group were free from rCDI at eight weeks post-treatment, compared with 60% in the placebo group. At 24 weeks post-treatment, 79% of the fecal microbiota group were still free from rCDI, compared with 53% in the placebo group, reinforcing the durable relief. 

ECOSPOR IV (SERES-013): An open-label extension study of ECOSPOR III and open-label program evaluated SER-109 in 263 adult participants with rCDI at the commercial dose to fulfill FDA requirements for the fecal microbiota safety database. The study duration for both cohorts was approximately 27 weeks, including a three-week screening period, an eight-week primary efficacy period and a 16-week follow-up period. Top-line results indicated that the safety profile was well tolerated, and there was a 91% sustained clinical response at eight weeks in the overall population. At 24 weeks post-treatment, 86% of patients treated with fecal microbiota experienced sustained clinical response. 

The most commonly reported side effects by fecal microbiota recipients, which occurred at a greater frequency than the placebo recipients, included abdominal bloating, fatigue, constipation, chills and diarrhea.
The dosing regimen of oral fecal microbiota is four capsules taken once daily for three consecutive days. The fecal microbiota contains live bacteria and is manufactured from human fecal matter that has been donated by qualified individuals. Although the donors and donated stool are tested for a panel of transmissible pathogens, fecal microbiota may carry a risk for transmitting infectious agents. It is also possible for fecal microbiota to contain food allergens; the potential for fecal microbiota to cause adverse reactions due to food allergens is unknown.

CDI is one of the most common healthcare-associated infections in the United States and is associated with 15,000 to 30,000 deaths annually. The leading cause of C. difficile is antibiotic use. Other factors that can increase the risk for CDI include being older than 65 years, hospitalization, nursing home residency, immunocompromise and/or a history of CDI. After recovering from CDI, individuals may get the infection again—often multiple times—a condition known as rCDI. The risk of additional recurrences increases with each infection and treatment options for recurrent CDI are limited. The administration of fecal microbiota is believed to facilitate restoration of the gut flora to prevent further episodes of CDI.

In July 2021, Seres entered into an agreement with Nestlé Health Science to jointly commercialize oral fecal microbiota in the United States and potentially Canada.

The FDA granted the application Priority Review, Breakthrough Therapy and Orphan Drug designations.

—GEN News Staff

Originally published by our sister publication Infectious Disease Special Edition