Acurx Announces Phase 2 Success and Phase 3 Readiness for Ibezapolstat in C. difficile Treatment

Acurx Pharmaceuticals, Inc., a biopharmaceutical company specializing in innovative antibiotics for difficult-to-treat bacterial infections, has announced promising developments following an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA). The meeting concluded with the FDA endorsing key elements necessary to advance ibezapolstat, Acurx's lead antibiotic candidate, into Phase 3 clinical trials for the treatment of Clostridioides difficile Infection (CDI).

The proposed Phase 3 trials will be non-inferiority, pivotal studies designed to compare ibezapolstat with standard-of-care vancomycin. Crucial factors such as protocol design, patient population, primary and secondary endpoints, and the size of the safety database have been agreed upon. The primary efficacy analysis will employ a Modified Intent-To-Treat (mITT) population, which aligns with the European Medicines Agency (EMA) requirements and will involve around 450 subjects. These subjects will be randomized in a 1:1 ratio to receive either ibezapolstat or vancomycin. The trial aims to determine ibezapolstat’s ability to achieve clinical cure of CDI two days after a 10-day oral treatment and to evaluate its potential to reduce CDI recurrence.

Acurx's Executive Chairman, Robert J. DeLuccia, expressed satisfaction with the outcomes of the FDA meeting, highlighting the milestone as essential for the company's progression into international Phase 3 trials. DeLuccia emphasized that the company now has a comprehensive roadmap not only for the Phase 3 program but also for filing a New Drug Application (NDA) for market approval.

The completed Phase 2 clinical trial of ibezapolstat consisted of an initial open-label single-arm segment (Phase 2a) followed by a double-blind randomized, active-controlled, non-inferiority segment (Phase 2b) at 28 U.S. clinical trial sites. The Phase 2a involved 10 patients treated with ibezapolstat, resulting in a 100% clinical cure rate. Following this, the Phase 2b segment involved 32 patients randomized to receive either ibezapolstat or vancomycin, with both treatments showing similarly high cure rates without significant safety concerns.

The multinational Phase 3 trial preparation is in progress, with the company planning to submit requests for guidance to initiate clinical trials in the European Union, the United Kingdom, Japan, and Canada. Acurx has been granted SME designation by the EMA, enabling the company to benefit from fee incentives and other support in the EU.

Ibezapolstat's promising results include a 96% Clinical Cure rate in the combined Phase 2 trials and no significant drug-related adverse events. The antibiotic is designed to target Gram-positive bacteria selectively, which includes C. difficile, while sparing other beneficial gut microbiota, thus maintaining a healthy gut microbiome.

Phase 2 trials also revealed important microbiome changes and bile acid metabolism dynamics. During treatment with ibezapolstat, there was an overgrowth of beneficial gut microbiota and an increase in secondary bile acids, which are known to provide resistance against C. difficile colonization. These findings suggest that ibezapolstat may reduce CDI recurrence compared to vancomycin.

Having received FDA QIDP and Fast-Track Designation, ibezapolstat is now positioned to enter Phase 3 trials, with the company optimistic about its potential to become a significant treatment for CDI. Acurx continues to focus on its goal of developing effective antibiotics that address the urgent need for new treatments for serious bacterial infections.