One phase 2 study showed that RBX2660, a microbiota-based drug comprised of human stool, was effective in 77.8% of patients.
Dale Gerding, MD
An enema-administered microbiota-based treatment (RBX2660) is effective and safe for preventing recurrent Clostridium difficile infection (CDI) in patients with a history of recurrent CDI, according to findings presented at Anaerobe 2018 in Las Vegas, Nevada, held July 9-12, 2018.
RBX2660 is comprised of a single-dose of 50 g human stool contained in a 150 mL liquid suspension. The treatment includes spore and non-spore-forming microbes and is administered via ready-to-use enema.
“Rebiotix is seeking FDA Biologics License Application (BLA) approval for a microbiota replacement product [RBX2660] that will be readily available to physicians and has been demonstrated to be both safe and effective in preventing further recurrence of CDI in patients who have already had multiple CDI episodes,” study author and presenter Dale Gerding, MD, of the Veterans Affairs Hospital in Hines, IL, told MD Magazine®. “Current ‘stool bank’ purchasing sites are not gathering sufficient data to meet these FDA requirements for safety and efficacy that are needed to assure physicians and patients. These safety and efficacy issues will be addressed through the FDA approval process.”
The analysis Gerding presented is a synthesis of 2 datasets: 1) a phase 2B randomized controlled trial with an open-label option for participants with treatment failure (PUNCH CD), and 2) a phase 2 open-label trial with controls who had a history of antibiotic treatment (PUNCH SOS). In both trials, participants had ≥2 CDI recurrences following a primary episode or had ≥2 CDI episodes which resulted in hospital admission. Study investigators administered 1-2 doses of RBX2660 exactly 7 days apart, with treatment failures resulting in the administration of up to 2 open-label active treatment doses.
Successful treatment was defined as the absence of C. difficile diarrhea without requiring anti-infective or fecal transplant retreatment through 56 days following the last enema administration. Treatment failure was defined as a positive C. difficile stool test, need for CDI retreatment, presence of diarrhea with or without other CDI symptoms within 8 weeks following last enema therapy, and no other identifiable cause for diarrhea.
In the PUNCH SOS study, patients receiving 2 doses of RBX2660 (n = 136) were compared with historical controls (n = 110). In the PUNCH CD study, patients were randomized to either 2 doses of RBX2660, 2 doses of placebo, or 1 dose of RBX2660 plus 1 dose of placebo. A total of 369 recurrent CDI patients were included in both trials.
Patients receiving ≥1 blinded RBX2660 treatment dose experienced a significantly higher success rate compared with patients receiving placebo (66.7% vs 45.5%, respectively; P <.05). In the open-label study, administration of ≥1 RBX2660 dose was effective in 77.8% of patients. No unanticipated adverse events were found, with most events being attributed to gastrointestinal issues within 8 weeks following treatment.
“The RBX2660 trials are underway and will gather not only data on safety and efficacy but will also correlate clinical outcomes with changes in the microbiome of the recipient subjects who are administered RBX2660 vs placebo,” Gerding concluded.
The study, “The Microbiota-based Drug RBX2660 is Efficacious and Safe in Patients with Recurrent Clostridium difficile Infections: Results from 2 controlled Clinical Studies,” was presented at the Anaerobe 2018 Congress in Las Vegas, NV, on July 12, 2018.
Disclosure: Dale Gerding is a member of the Scientific Advisory Board for Rebiotix, Merck, Actelion, Summit, and DaVolterra and also serves as Medical Officer for Rebiotix.