Acurx Pharmaceuticals, Inc. has announced positive regulatory guidance from the European Medicines Agency (EMA) for its ibezapolstat Phase 3 program in treating Clostridioides difficile Infection (CDI). The EMA's feedback, received during its Scientific Advice Procedure, confirms that the submitted clinical, non-clinical, and Chemistry Manufacturing and Controls (CMC) information package supports the advancement of ibezapolstat into Phase 3 trials. This guidance paves the way for Acurx to potentially secure marketing authorization in Europe, complementing the positive feedback previously received from the U.S. Food and Drug Administration (FDA).
EMA's Positive Guidance
The EMA's positive written responses included guidance on ibezapolstat's regulatory pathway for a Marketing Authorization Application in CDI. This endorsement from the EMA, combined with the FDA's agreement on Phase 3 readiness, positions Acurx to commence its international Phase 3 registration program.
Bob DeLuccia, Executive Chairman of Acurx, expressed his appreciation for the EMA's constructive suggestions, stating, "We are very pleased with the latest favorable communications from both regulatory agencies which provide a straightforward international roadmap for conduct of our Phase 3 program and ultimate requirements for a US NDA (New Drug Application) submission and EU Marketing Authorization Application."
Phase 3 Trial Design
The planned Phase 3 program will consist of two pivotal, non-inferiority trials comparing ibezapolstat to vancomycin, the current standard of care for CDI. Key elements of the trials have been confirmed, including the protocol design, patient population, primary and secondary endpoints, and the size of the registration safety database. The primary efficacy analysis will be performed using a Modified Intent-To-Treat (mITT) population, with an estimated 450 subjects randomized in a 1:1 ratio to either ibezapolstat or vancomycin in the initial trial.
The trial design will assess ibezapolstat's ability to achieve Clinical Cure of CDI, measured two days after ten days of oral treatment, and its potential effect on reducing CDI recurrence. In the event non-inferiority to vancomycin is demonstrated, further analysis will be conducted to test for superiority.
Ibezapolstat's Potential Impact
Clostridioides difficile infection remains a significant medical challenge, with recent estimates suggesting approximately 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. The recurrence rate for current antibiotics used to treat CDI ranges between 20% and 40%. Ibezapolstat, a novel, orally administered antibiotic with a Gram-Positive Selective Spectrum (GPSS), is designed to minimize disruption of the gut microbiome, potentially reducing the likelihood of CDI recurrence.
Phase 2 Clinical Trial Results
Ibezapolstat's Phase 2 clinical trial, which included both Phase 2a and Phase 2b segments, demonstrated promising results. The overall observed Clinical Cure rate in the combined trials was 96% (25 out of 26 patients). Ibezapolstat was well-tolerated, with only mild, drug-related gastrointestinal adverse events reported. Furthermore, Phase 2 data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat, along with the overgrowth of healthy gut microbiota.
Next Steps
Acurx is preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, followed by requests in the United Kingdom, Japan, and Canada. The company believes that the mutually consistent feedback from both the EMA and FDA provides a clear international roadmap for the conduct of its Phase 3 program and the requirements for a US NDA submission and EU Marketing Authorization Application.
