Background: Recurrent Clostridioides difficile infection (rCDI) is an urgent public health threat. RBX2660 is a standardized, stabilized, investigational microbiota-based live biotherapeutic that has been evaluated in 5 prospective clinical trials. Eligibility criteria in clinical trials are often narrowly defined, excluding broader patient populations. Herein, we report a retrospective analysis of safety and efficacy of RBX2660 given under US Food and Drug Administration enforcement discretion (ED) in a cohort with broad eligibility criteria.

Methods: Participants were ≥18 years of age with rCDI and received RBX2660 rectally. The investigator determined the number of doses administered. Participant data were collected from electronic health records. The primary safety set (PSS) population included participants who had not been previously treated with RBX2660 and who had continuously comprehensive medical records for 6 months after therapy. Safety, treatment success (absence of CDI recurrence within 8 weeks post-RBX2660), and clinical response duration were evaluated.

Results: Ninety-four participants were enrolled from 5 sites between November 2015 and September 2019. Comorbid conditions included gastroesophageal reflux disease (47.9%), irritable bowel syndrome (17%), gastritis (11.7%), constipation (8.5%), microscopic colitis (7.4%), diverticulitis (6.4%), Crohn’s disease (5.3%), and ulcerative colitis (4.3%). Sixteen percent of patients were using concomitant immunosuppressants such as glucocorticoids (7%) and monoclonal antibodies (6%) at the time of RBX2660 administration. Sixty-four of the 94 participants were in the PSS, with a treatment success rate of 82.8% (53 of 64 participants). No difference was observed between participants who received 1 dose (83.3%; 20 of 24 participants) versus 2 doses (82.5%; 33 of 40 participants) after the qualifying CDI diagnosis. For those patients who initially had a response, sustained clinical response to 6 months was 88.7% (47 of 53 participants). Safety outcomes were comparable to prospective studies for RBX2660, with most adverse events (92.2%) being mild to moderate in severity, including those in participants who had immune-mediated or autoimmune disorders and nonspecific inflammation conditions.

Conclusions: In this retrospective analysis, RBX2660 administered to participants under ED demonstrated high clinical efficacy for reducing rCDI with a sustained clinical response to 6 months. Safety results were consistent with prospective trials. The results substantiate the potential safety and efficacy of RBX2660 in real-world populations with common rCDI comorbidities.