New Data Shows the Efficacy, Durability of RBX2660 for Recurrent C Difficile Infections

Robert Orenstein, DO

RBX2660, a live microbiome therapeutic, has shown efficacy, safety, and durability in treating patients with recurrent Clostridium difficile infections (CDI), according to new data from a phase 2 study.

A team, led by Robert Orenstein, MD, Division of Infectious Diseases, Mayo Clinic in Arizona, evaluated the safety, efficacy, and durability of RBX2660 for patients with recurrent C difficile infections.

RBX2660

RBX2660 is a standardized, stabilized, investigational microbiota-based live therapeutic. Currently, standard-of-care for patients with recurrent C difficile infections is antibiotics, with consideration of fecal microbiota transplantation (FMT) following multiple recurrences.

However, it is unlikely the US Food and Drug Administration (FDA) approves FMT as a viable treatment, paving the way for live microbiome therapeutics like RBX2660 to fill the gap.

“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 authors wrote.

The Trial

In the prospective, multicenter, open-label phase 2 study, the investigators examined patients who had experienced either at least 2 recurrences of CDI treated by standard-of-care antibiotic therapy following a primary CDI episode or at least 2 episodes of severe CDI requiring hospitalization.

Each patient received 2 doses of RBX2660 rectally 7 days apart.

The investigators defined treatment success as the absence of CDI diarrhea without needing retreatment for 8 weeks after completing the study treatment.

There was also a historical control group included in the analysis, with matched inclusion and exclusion criteria identified from a retrospective chart review of patients treated with standard-of-care antibiotics for recurrent CDI who matched key criteria for the study.

The investigators compared the treatment success of the study drug to the historical control group as the primary objective, with the safety profile of RBX2660, including adverse events and CDI occurrence through 24 months after treatment as the secondary objective.

They also sequenced fecal samples from the RBX2660 cohort to evaluate microbiome composition and functional changes from before to after treatment.

Treatment Success

Overall, the treatment success rate was 78.9% (n = 112) in the RBX2660 group, compared to 30.7% (n = 23) for the historical control cohort (P <0.0001).

In the post-hoc analysis, 91% (n = 88) of evaluable RNX2660 responders remained CDI incidence-free for the 24 months following treatment.

Safety and Durability

The treatment was also well-tolerated, with mostly mild to moderate adverse events.

Finally, the composition and diversity of the responders fecal microbiome significantly changed throughout the duration of the study to become more similar to RBX2660. These changes were durable for 24 months following treatment.

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

The study, “Durable reduction of Clostridioides difficile infection recurrence and microbiome restoration after treatment with RBX2660: results from an open-label phase 2 clinical trial,” was published online in BMC Infectious Diseases.