Investigational Microbiota-based Therapy Bests Placebo to Reduce Recurrence of C. difficile Infection

Clostridioides difficile

A single dose of an investigational microbiota-based live biotherapeutic used to treat recurrent Clostridioides difficile infection (rCDI) showed consistent efficacy as early as a first recurrence of the infection, according to results of the phase 3 PUNCH CD3 clinical trial.

A potential first-in-class treatment, RBX2660 is being studied to deliver a broad consortium of diverse microbes directly to the gut to reduce rCDI.

“C. difficile infection is a global public health threat that requires immediate action to halt the unrelenting cycle of recurrence, said Paul Feuerstadt, MD assistant clinical professor of medicine, Yale University School of Medicine, and RBX2660 clinical trial investigator in a statement from Ferring Pharmaceuticals. “While necessary to treat initial infection, antibiotics are also a predominant risk factor for recurrence because they can disrupt the gut microbiome, leaving the current treatment paradigm for recurrent infection incomplete.”

The phase 3, prospective multicenter randomized, double-blinded, placebo-controlled PUNCH CD3 trial evaluated the efficacy and safety of RBS2260 vs placebo in preventing rCDI. Investigators enrolled adults aged ≥18 years who had at least one recurrence after a primary episode of CDI. Follow-up for the efficacy analysis was 8 weeks and for the safety analysis was 6 months.

The trial successfully met its primary endpoint, with RBX2260 demonstrating superior efficacy vs placebo (70.4% and 58.1%, respectively) at 8 weeks post treatment. The RBX2260 safety profile was comparable to that seen with placebo. The posterior probability of superiority was 98.6%, exceeding the 97.5% minimum threshold and reaching statistical significance.

In addition, researchers reported a relative reduction of recurrence of 29.4% with RBX2260 vs placebo. The majority of treatment emergent adverse events with RBX2260 were mild to moderate in nature and similar to placebo.

“People who suffer from C. difficile infection are devastated when they experience recurrence. Patients have told me that they felt hopeless when the infection returned again and again despite multiple courses of antibiotic treatment,” said Chrstine Lee, clinical professor, department of pathology and laboratory medicine, UBC Faculty of Medicine and RBX2660 clinical trial investigator in the company statement. “They believed that the infection would never go away.

"The findings from this pivotal Phase 3 trial of RBX2660 are very encouraging to both patients and healthcare providers, providing hope this potential new treatment could make a meaningful difference in the lives of patients with recurrent C. difficile infection."

The PUNCH CD3 trial results were presented at Digestive Disease Week 2021. RBX2660 has been granted Fast Track, Orphan, and Breakthrough Therapy designations from the US Food and Drug Administration, according to the Ferring statement.

The RBX2260 trial, the statement notes, is the largest to date in the field of microbiome-based therapeutics. There are 6 trials in the 10-year development program that have enrolled >1000 patients. The Ferring release also states that 2 of those trials currently are the only ones to include 2 years of safety follow-up.