Investigational oral enzyme prevents C. difficile infection after IV antibiotics

SYN-004, or ribaxamase, significantly reduced the rate of Clostridium difficile infection in patients receiving certain IV beta-lactam antibiotics in a phase 2b clinical trial, the manufacturer announced.

SYN-004 (ribaxamase; Synthetic Biologics) is an oral enzyme that degrades certain IV beta-lactam antibiotics in the GI tract to protect the gut microbiome and prevent C. difficile infection, antibiotic-associated diarrhea and the emergence of antibiotic-resistant organisms.

“These trial results provide a compelling demonstration of the potential of ribaxamase to help address the serious health impacts associated with CDI and infections from other opportunistic bacteria resulting from dysbiosis of the gut microbiome,” Joseph Sliman, MD, senior vice president of clinical and regulatory affairs at Synthetic Biologics, said in a press release. “More than 453,000 patients are diagnosed with CDI annually in the U.S., resulting in approximately 29,000 deaths as well as significant and sometimes prolonged illness. Ribaxamase has the potential to shorten hospital stays, diminish morbidity and mortality and reduce the emergence of antibiotic-resistant organisms in the gut microbiome by protecting patients from primary C. difficile infection resulting from IV antibiotic use.”

The study, which was supported by the CDC, was a randomized, double blind, placebo-controlled trial involving 412 patients. Preliminary analysis showed two patients who received ribaxamase vs. seven patients who received placebo developed CDI, with a 71.4% relative risk reduction in the treatment group (P = .045). Adverse events were similar between groups.

In addition, preliminary analysis of exploratory endpoints showed ribaxamase significantly reduced new colonization by vancomycin-resistant enterococci compared with placebo (P = .0002).

Moreover, preliminary analysis of a secondary endpoint agreed upon by the FDA suggested a trend toward reduction of antibiotic-associated diarrhea from all causes with ribaxamase, mostly due to the reduction of CDI (P = .13).

The company plans to present additional data later this year, including evidence regarding the ability of ribaxamase to prevent antimicrobial resistance from emerging in the gut microbiome, according to the press release.

“These findings ... help further our goals to bring the first ever microbiome-focused therapeutic to patients and to help illuminate the potential of this drug class to address serious diseases and public health concerns,” Jeffrey Riley, president and CEO of Synthetic Biologics, said in the press release. “We expect to share additional data from exploratory endpoints in the coming months and look forward to continuing ongoing and productive discussions with both the FDA and CDC on the protocol for phase 3 pivotal trials for ribaxamase.”

Disclosures: Riley and Sliman are employed by Synthetic Biologics.