Live Microbiome Therapeutic Found Safe, Effective Treating Recurrent C Difficile Infection

Data from a phase 2 study of a potential first-in-class microbiota-based live biotherapeutic showed efficacy, safety, and durability with the treatment in patients with recurrent Clostridium difficile infection (CDI).

The study, published online in BMC Infectious Diseases, analyzed treatment with RBX2660 for patients with recurrent CDI (rCDI). RBX2660 is a standardized, stabilized, novel microbiota-based live therapeutic.

The current standard-of-care for patients with rCDI is antibiotics, whereas fecal microbiota transplantation (FMT) is considered after multiple CDI recurrences. The study investigators noted that it is unlikely that the FDA will approve FMT as a viable treatment for CDI, which leaves live microbiome therapeutics, such as RBX2660, to address this unmet need.

“Using microbial consortia to restore the composition and diversity of patients’ intestinal microbiota is a promising strategy for preventing rCDI, with FMT gaining traction, despite a lack of standardization of process, product, or procedure,” the study authors wrote.

For the prospective, multicenter, open-label phase 2 study, the researchers evaluated patients with at least 2 recurrences of CDI who were administered standard-of-care antibiotic therapy after a primary CDI episode, or who experienced a minimum of 2 episodes of severe CDI that required hospitalization. Each patient was administered 2 doses of RBX2660 rectally 7 days apart.

The investigators defined treatment success as the absence of CDI diarrhea without requiring retreatment for 8 weeks following completion of RBX2660. The analysis compared the study drug group with a historical control group with matched inclusion and exclusion criteria identified from a retrospective chart review of patients treated with standard-of-care antibiotics for recurrent CDI.

The study’s primary objective was to compare treatment success with RBX2660 with the historical control group, as well as to evaluate the safety profile of RBX2660, including adverse events (AEs) and CDI occurrence through 24 months following treatment. The investigators also sequenced fecal samples from the RBX2660 treatment group to evaluate microbiome composition and functional changes from before and after treatment.

The treatment success rate was 78.9% (n = 112) in the RBX2660 cohort versus 30.7% (n = 23) in the historical control group (P <0.0001). A post-hoc analysis found that 91% (n = 88) of evaluable patients who responded to RBX2660 remained incidence-free of CDI for the 24 months following treatment.

Additionally, RBX2660 was found to be well-tolerated, with mostly mild to moderate AEs reported. The composition and diversity of the fecal microbiome among responders significantly changed to become more similar to RBX2660 over the duration of the study, with these changes found to be durable for 24 months post treatment.

“In this phase 2 trial, RBX2660 was safe and effective for reducing rCDI recurrence as compared to a historical control group,” the study authors wrote. “Microbiome changes are consistent with restorative changes implicated in resisting C. difficile recurrence.”