The Role of Microbiome-Based Therapeutics in Clostridioides difficile Infection: Durable, Long-Term Results of RBX2660.

ABSTRACT

A recently published manuscript described findings from a phase 2 open label study of the microbiota-based live biotherapeutic product RBX2660 in patients with two or more previous recurrent Clostridioides difficile infection (rCDI) episodes, and described long-term safety and sustained treatment success through 24 months. As previous studies have typically focused on short-term clinical outcomes, these new data provide insight into the tolerability, safety, and efficacy of RBX2660 over the long term. When microbiota-based products were first evaluated, the long-term efficacy and safety were principal concerns of the United States Food and Drug Administration. Microbiota-based live biotherapeutic products (LBPs) represent an emerging approach to the management of CDI and perhaps other gastrointestinal and medical conditions whose pathogenesis is defined by microbial dysbiosis. RBX2660 is a human-derived, broad consortium microbiota-based LBP that consists of a population of microbes obtained from healthy stool donors and may reflect the symbiotic nature of a healthy colonic microbiome. RBX2660 is rectally administered and does not require sedation or special preparation of the recipient. Potential advantages of the rectal administration of RBX2660 include the ease of administration and lack of need for any bowel preparation, which may benefit those who are frail, have swallowing issues, or cannot take bowel laxative preparations. In this multicenter prospective trial of rCDI, patients who achieved treatment success 8 weeks after receiving RBX2660 continued to have a sustained clinical response over the course of long-term follow-up, with more than 90% of treatment responders remaining CDI-free at 6, 12, and 24 months. Following receipt of RBX2660, the gut microbiota of those with treatment success were restored from a dysbiotic state to become more diverse and similar to RBX2660 composition. The restoration of the microbiota occurred as early as 7 days after RBX2660 administration and remained stable through the 24-month analysis. No new adverse outcomes were observed during the prospective assessment, and the safety profile of RBX2660 was consistent with previous studies. Based on the clinical studies, RBX2660 will most likely benefit those with ≥ 1 rCDI episode or those who are at a high risk of subsequent rCDI, such as patients who have comorbid conditions including renal disease, heart disease, or inflammatory bowel disease, or who are immunosuppressed. The role of microbiome-based therapeutics in 47 Clostridioides difficile infection Durable, long-term results of RBX2660 (MP4 511833 KB).