Ibezapolstat Preserves Beneficial Microbiome in Multiply-Recurrent C. difficile, Acurx Data Show

Acurx Pharmaceuticals announced new data showing its antibiotic ibezapolstat preserves beneficial gut bacteria in patients with multiply-recurrent Clostridioides difficile infection (rCDI), even after multiple prior treatments with standard-of-care antibiotics vancomycin and fidaxomicin. The findings, presented at the 18th Biennial Congress of the Anaerobe Society of the Americas, suggest ibezapolstat could allow microbiome repopulation and prevent recurrence, potentially shifting the treatment paradigm from two agents to one.

Studies performed at the University of Houston revealed that beneficial bacterial taxa persist in fecal samples from rCDI patients despite previous courses of vancomycin and/or fidaxomicin. In laboratory experiments, ibezapolstat outperformed both comparators in killing C. difficile in biofilm models and did not cause vancomycin-resistant enterococci (VRE) overgrowth, a problem observed with vancomycin.

The principal investigator for microbiology and microbiome aspects of the ibezapolstat clinical program stated that it was previously unknown whether repeated standard-of-care antibiotics destroyed the organisms responsible for bile acid metabolism and protection against recurrence. The new data indicate sufficient numbers of such bacteria are preserved to allow regrowth when treatment consists of a highly selective antibiotic like ibezapolstat. He added that ibezapolstat was highly effective at killing C. difficile in co-culture with Enterococcus in both planktonic and biofilm conditions, actually outperforming fidaxomicin in biofilm killing effects.

The executive chairman of Acurx said these data provide scientific support for an upcoming trial in multiply-recurrent CDI. The program begins with a 20-patient, open-label pilot study enrolling patients with at least three CDI episodes in the past 12 months, which will inform a planned active-controlled Phase 3 registration trial in rCDI. Upon successful completion, Acurx plans to request FDA approval for treatment and prevention of rCDI under the FDA’s Limited Population Pathway for Antibacterial and Antifungal Drugs. The company believes ibezapolstat has the potential to be the first agent to demonstrate clinical success in both acute CDI treatment and reduction of recurrence in rCDI, shifting the paradigm from two agents to one.

With consistent feedback from both the FDA and the European Medicines Agency, Acurx is positioned to commence an international Phase 3 registration program in the broader acute CDI patient population. The company has previously received FDA Qualified Infectious Disease Product (QIDP) and Fast-Track designations, as well as SME designation from the EMA. Trial start-up activities for the rCDI pilot have been initiated, with the first patient expected to enroll in the next quarter.