Follow-up results from Phase IIb clinical trials demonstrating the efficacy of Synthetic Biologics ’ ribaxamase (SYN-004) in protecting the gut microbiome in patients receiving IV ceftriaxone were presented at the 2018 European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). These results showed that the gut microbiome of patients receiving ceftriaxone and a placebo was significantly disrupted (P<0.001), whereas in those receiving ribaxamase the microbiome was not disrupted.
Synthetic Biologics is positioning ribaxamase for the prevention of Clostridium difficile infections (CDIs) following treatment with beta-lactam antibiotics. Previous results from the Phase IIb clinical trial found that ribaxamase reduced the relative risk of CDI by 71% in 412 patients receiving ceftriaxone for lower respiratory tract infections and reduced colonization with vancomycin-resistant enterococci (VRE) compared to placebo (P=0.045; P=0.0002).
In this follow-up study, researchers studied the microbiome in a total of 650 fecal samples collected from patients before, immediately after, and four weeks following a full course of treatment with ceftriaxone. 16s RNA sequencing analysis was used to measure changes in the microbiome, a sub-set of fecal samples underwent whole genome shotgun sequencing which revealed the lower level of antimicrobial resistance (AMR) genes in the ribaxamase group, thereby demonstrating that ribaxamase can also reduce the impact that beta-lactam antibiotics have on the development of AMR in the gut microbiome.
The microbiome is currently a popular target for pipeline therapeutics aiming to stop recurrence of CDIs. A procedure known as fecal microbe transplant (FMT) has shown promise in reducing CDI recurrence, although further clinical evidence of its effectiveness must be obtained before its widespread use.
KOLs interviewed by GlobalData believe that replenishing or maintaining a patient’s microbiome play a crucial role in preventing CDI recurrence. These latest results continue to provide evidence that ribaxamase is efficacious in protecting the gut microbiome from beta-lactam antibiotics, and Phase III trials scheduled to begin in 2019 aim to provide evidence this translates to protective efficacy of CDI in patients receiving IV ceftriaxone as well as other beta-lactam antibiotics.
Unlike other approaches to preventing CDIs, such as the vaccines currently in development by Pfizer and Valneva , ribaxamase does not require an extended period of administration prior to exposure to C. difficile. Therefore this product can be positioned to directly protect patients at high risk of CDI or CDI recurrence who are receiving beta-lactam antibiotics. GlobalData believes that due to its unique mechanism of action (MOA), ribaxamase could be positioned as being more convenient prophylactic option to the vaccines currently in development.
GlobalData (2018). Expert Insight: J&J Discontinues Development for C. difficile Antibiotic, Cadazolid, April 2018, GDHC1720EI
GlobalData (2017), Expert Insight: Discontinuation of Sanofi’s C. difficile Vaccine Program Could Spell Good News for Pfizer and Valneva, December 2017, GDHC1496EI
GlobalData (2017). OpportunityAnalyzer: Clostridium difficile Infections (CDIs) – Opportunity Analysis and Forecasts to 2026, July 2017, GDHC070POA
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