Efficacy Outcomes of Fecal Microbiota, Live-jslm in Preventing Recurrent Clostridioides difficile Infection from Seven Clinical Studies

Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections in the US, and recurrence remains a major clinical challenge, as standard-of-care antibiotics fail to prevent recurrence in up to one-third of cases. Fecal microbiota, live-jslm (RBL) is the first single-dose, microbiota-based product approved by the US Food and Drug Administration and Health Canada for the prevention of recurrent CDI (rCDI) following standard-of-care antibiotics. The RBL clinical development program is the largest to date for any microbiota-based product, encompassing seven studies and enrolling over 1700 participants to evaluate the safety and efficacy of RBL in preventing rCDI. Although the RBL development program consistently evaluated both efficacy and safety outcomes across all studies, this review summarizes the study designs, with a primary focus on the efficacy outcomes. The program consists of randomized controlled trials, open-label cohorts, retrospective analyses, and real-world data, each contributing unique insights across different patient populations and treatment settings. All studies enrolled adults aged ≥ 18 years with rCDI who received antibiotics for their enrolling CDI episode before RBL administration. Most studies administered RBL rectally, except for an open-label study and a retrospective study, which evaluated colonoscopic administration of RBL. Treatment success was evaluated at 8 weeks, and sustained clinical response was evaluated at 6 or 24 months after RBL and/or placebo administration, depending on the study design. Overall, the study designs for all seven studies were consistent, with slight differences between number of CDI episodes (specifically, 2 studies allowed enrollment after the first CDI recurrence), blinding, controls, and administration routes. Efficacy data of RBL reported across all studies consistently demonstrated RBL is efficacious for the prevention of rCDI in a broad adult population. ClinicalTrials.gov. NCT01925417; NCT02299570; NCT02589847; NCT03244644; NCT03931941; NCT05831189. Antibiotics used to treat bacterial infections can also damage good bacteria in the gut (dysbiosis). When these good bacteria are damaged, a bacterium called Clostridioides difficile can overgrow and release toxins that harm the colon. This can cause severe diarrhea and may become life-threatening. Antibiotics used to treat C. difficile infection contribute to dysbiosis and increase the chance the infection will return. Microbiota-based products are treatments comprising a wide variety of gut microbes. They help restore the natural balance of bacteria in the gut and have been shown to prevent C. difficile infection from returning. RBL, also known as REBYOTA® or fecal microbiota, live-jslm, is one of these microbiota-based products developed to prevent recurrent C. difficile infection in adults. The RBL clinical development program is currently the largest group of studies for any microbiota-based product. More than 1700 people have taken part in these studies to test the safety of RBL and its efficacy in preventing recurrent C. difficile infections. This review summarizes all the RBL studies and results seen so far. Across the different studies, which were similar in design and included a wide range of adult participants, RBL consistently helped prevent C. difficile infections from returning. Overall, the evidence shows RBL is effective for many adults at risk of recurrent C. difficile infection.