About Clostridium difficile Infection

With about 29,000 patient deaths a year, the U.S. Centers for Disease Control has termed Clostridium difficile (C. diff.) infection an urgent public health threat. Although estimates vary, there are between 500,000 and 700,00 cases of C. diff. infection in the U.S.

Risk Factors

  • Antibiotic use
  • Older age (> 65 years)
  • Exposure to health care facilities
  • Severe underlying disease
  • Compromised immune response

The Problem of Recurrence

Antibiotic therapy is the standard treatment following an initial diagnosis C. diff. However, approximately 25%1 of patients initially cured will experience a recurrence. Each recurrence predisposes to further recurrence. After two or more episodes of recurrence, the risk of subsequent recurrence may reach 65%.1

Breaking the Cycle of Recurrence

In healthy individuals, the microbial balance in the gut microbiota prevents the development of symptomatic C. diff. infection. However, antibiotics disturb this balance, allowing C. diff. infection to colonize the large intestine of people at risk of infection.2

The Potential of Microbiota-Based Therapies in the MRT™ Drug Platform

Rebiotix Microbiota Restoration Therapy (MRT)  drug platform presents the possibility to change the therapeutic landscape for recurrent C. diff. infection.

A Phase 2 randomized placebo-controlled double-blind study of lead MRT product, RBX2660, for recurrent C. diff. has completed enrollment. An oral formulation for C. diff. prevention and additional MRT™ drug platform drugs are under development.

Key Milestones

Rebiotix is making excellent progress in hitting prerequisite milestones for commercialization of RBX2660 for recurrent C. diff.:

  • PUNCH CD study
    • Prospective, Multi-center, Open-label
    • 40 subjects enrolled, 34 treated, 8 wk. primary endpoint prevention of recurrent C. diff with follow-up at 6 months
    • Designed for safety and efficacy
    • 1 dose delivered with a 2nd dose delivered if recurrence at < 8wks
    • Mean age 66.8 (Range: 26.7-89.6) years, Female 67.6%
      • 87.1% of subjects (n=27) were free of C. diff. recurrence at 8 weeks (one or two doses)
      • No additional recurrences of C. diff were observed in successfully treated patients following antibiotic treatment for other indications during the 6-month treatment period
      • No serious adverse events (SAEs) related to product or procedure
      • Most common AE’s were flatulence, abdominal pain/cramping, constipation, diarrhea – all self-limiting
      • Durable: Successfully treated subjects at 8 weeks remained C, diff-infection-free over the 6-month treatment period
  • PUNCH CD 2
    • Prospective, Multi-center, Randomized, Double-blind, Placebo-controlled with 133 patients enrolled
    • 107 patients received at least 1 dose of RBX2660; Three treatment arms, 8 wk. primary endpoint with 24 month follow-up
    • Designed to determine if one or two doses of RBX2660 was superior to placebo
    • Median age 63 (Range: 18-92) years, Female 59.8%
      • Single dose RBX2660 performed significantly better than placebo (p= 0.048) (67 show % success vs. 46 % Placebo)
      • No difference between single dose and 2 fixed doses 7 days apart
      • Adverse Events were primarily gastrointestinal including diarrhea, abdominal pain, flatulence, constipation, nausea
      • 90% Durability for patients successfully treated with RBX2660 at a mean follow-up time of 398 days (13.3 months), range [61 – 734] days

Special FDA Designations for RBX2660:

  • Fast Track – May 2013
  • Orphan Drug – March 2014
  • Breakthrough Therapy – October 2015

References

  1. Kelly CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012; 18 (Suppl. 6): 21–27.
  2. Theriot CM, Young VB. Interactions Between the Gastrointestinal Microbiome and Clostridium difficile. Annu Rev Microbiol. 2015;69:445-61.