By Ajay V. Patil
Clostidium difficile – A serious healthcare associated infection
Clostridium difficile infection is a threatening infection (453,000 infections and close to 29,000 deaths in the United States each year) and it is associated with commonly used intravenous (IV) beta-lactam antibiotic treatment. Beta-lactam antibiotics are often the treatment of choice for hospitalized patients with infections; they include commonly used penicillin and cephalosporin antibiotics (like ceftriaxone). These antibiotics can cause harmful effects in the intestinal tract especially disturbing the gut microbiome which is important for prevention of C.difficile infection.
SYN004 – Fighting infection by protecting healthy microbiome
SYN-004 (ribaxamase) is an oral β-lactamase designed to be coadministered with intravenous antibiotics. It is developed by Synthetic Biologics Inc., a company focused on therapeutics benefiting through preserving healthy microbiome. Ribaxamase reportedly degrades excess-lactam antibiotic present in the small intestine. This results in keeping the natural balance of the gut microbiome intact to prevent C.difficile infection, other antibiotic-associated diarrheas, pathogenic overgrowth and the development of antimicrobial resistance (AMR).
Phase I and phase IIa studies
Phase I clinical studies showed that, ribaxamase was well tolerated compared to a placebo group and displayed negligible systemic absorption. In order to confirm the mechanism of action (β-lactam degradation in small intestine) phase IIa clinical studies were performed in subjects with functioning ileostomies (allowing serial sampling of their intestinal chime). Ribaxamase showed near complete degradation of ceftriaxone (below the level of quantitation) in the intestines of all subjects in both phase I & IIa studies. Coadministration of oral ribaxamase with intravenous ceftriaxone did not change plasma levels of ceftriaxone. Activity of this pH-dependent, delayed-release formulation of ribaxamase was not hampered in the presence of the proton pump inhibitor esomeprazole as shown in another coadministration study.
Positive phase III talks with FDA
Synthetic Biologics Inc. recently announced successful completion of an End-of-Phase II meeting with the U.S. FDA to discuss development of SYN-004 (ribaxamase) as the prophylactic for antibiotic-mediated C.difficile infection. FDA has proposed criteria for Phase III clinical efficacy and safety. If achieved, FDA may support its submission for marketing approval on the basis of a single Phase III clinical trial. Although final agreement is contingent on FDA evaluation of a detailed Phase III clinical trial protocol.
Development of such efficient prophylactic therapies which work through healthy microbiome preservation will provide new hope against serious and emerging infections around the globe.
- ClinicalTrials.gov under NCT02419001 and NCT02473640
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