Positive data have been reported from a phase 2b study of ribaxamase (SYN-004, Synthetic Biologics, Inc.), a first-in-class oral enzyme designed to protect the gut microbiome from the disruption caused by certain intravenous (IV) beta-lactam antibiotics. Several exploratory endpoints evaluated the ability of ribaxamase to protect the gut microbiome from colonization by opportunistic bacteria, such as Clostridium difficile and other antibiotic-resistant pathogens.
The randomized, double-blind, placebo-controlled, proof-of-concept study was intended to evaluate the efficacy of ribaxamase in preventing the onset of primary C. difficile infection (CDI), antibiotic-associated diarrhea (AAD), and the emergence of antibiotic-resistant organisms in patients hospitalized with lower respiratory infections and undergoing treatment with IV ceftriaxone. A total of 412 subjects were randomly assigned to receive 150 mg of ribaxamase or placebo once daily on day 1 and until 72 hours after their last treatment of IV ceftriaxone.
The study met its primary endpoint of significantly reducing CDI in this patient population. Preliminary analysis of the data indicated two confirmed cases of CDI in the ribaxamase group compared with seven cases in the placebo group. Patients treated with ribaxamase achieved a 71% relative risk reduction (P = 0.045) in CDI rates compared with those given placebo. Adverse events were comparable between the two cohorts.
Preliminary data also indicated a significant reduction in new colonization by vancomycin-resistant enterococci in patients treated with ribaxamase compared with those given placebo (P = 0.0002). With agreement from the FDA, the study included a secondary endpoint to assess the ability of ribaxamase to reduce the incidence of AAD from all causes. A preliminary analysis of these data suggested a trend toward such a reduction (P = 0.13), which was due, for the most part, to the reduction of CDI.
Ribaxamase is designed to degrade certain IV beta-lactam antibiotics in the gastrointestinal tract and to maintain the natural balance of the gut microbiome for the prevention of CDI, AAD, and the emergence of antibiotic-resistant organisms.
Source: Synthetic Biologics; January 5, 2017.