Phase 2 Results: Microbiota-Based RBX2660 Safe, Efficacious for Preventing C diff Recurrence
RBX2660, a microbiota-based drug, was safe and efficacious for preventing recurrent C diff infection with clinical durability to 24-months after treatment, independent of age or sex.
With astronomical treatment costs and a mortality rate some studies estimate at around 36%, there is an urgent need for novel agents to prevent recurrence of Clostridioides difficile infection (CDI).
Currently approved agents are associated with high recurrence rates, which can lead to increased readmissions. But a new commercially prepared, standardized, fecal microbiota suspension preparation that is packaged into a single-administration, ready-to-use enema bag may be an option.
Investigators at IDWeek 2019 presented the final, 24-month analysis of data from a phase 2 open-label trial of RBX2660 for the prevention of CDI recurrence. Patients with multi-recurrent CDI were enrolled in the multicenter study and received > 2 doses of RBX2660 delivered via enema 7 days apart.
The research team defined efficacy as absence of CDI recurrence through 56 days after the last dose, and durability as continued absence of CDI episodes beyond 8 weeks. Results were compared with the 8-week recurrence-free rates for a historical control cohort that received standard-of-care antibiotic therapy.
Participant stool samples were collected prior to and for up to 720 days after treatment, and safety and durability assessments were performed at 3, 6 ,12, and 24 months. Investigators assessed microbiome changes via shallow shotgun sequencing.
A total of 503 stool samples from 110 participants were analyzed. At 8 weeks, RBX2660 efficacy in preventing CDI recurrence (78.9%;112/142) was higher than the CDI-free rate in the historical control group (30.7%, 23/75; p< .0001). Neither age nor sex affected efficacy.
Ninety-five participants achieved treatment success at 8 weeks and were eligible for long-term durability evaluation. Eight of them experienced a new CDI episode by the 24-month follow-up, for an overall durability of 91.6%.
“Within 7 days of treatment, the relative abundance of Bacteroidia and Clostridia remained shifted higher than pre-treatment levels while Gammaproteobacteria and Bacilli declined sharply after treatment, and these changes persisted to at least 24 months,” investigators reported.
The safety profile of RBX2660 was also consistent with previous reports.
“RBX2660, a microbiota-based drug, was safe and efficacious for preventing rCDI with clinical durability to 24-months after treatment, independent of age or sex, and RBX2660 durability associated with durable microbiome shifts from pre-treatment to a healthier composition,” the research team concluded.
Ken Blount, PhD, chief scientific officer at Rebiotix, a Ferring Company, discussed the trial results and plans for next steps with Contagion® at IDWeek (see video).
The study, A Long Time Coming: Final Two-Year Analysis of Efficacy, Durability, and Microbiome Changes in a Controlled Open-Label Trial of Investigational Microbiota-Based Drug RBX2660 for Recurrent Clostridioides difficile Infections, was presented as a late breaking oral abstract on Thursday, October 3, 2019, at IDWeek in Washington, DC.