Acurx Advances Ibezapolstat Toward Phase 3 Following Positive FDA Feedback

Acurx Pharmaceuticals announced that the FDA has agreed with the overall design and evaluation criteria of its planned Phase 3 IBZ-ASPIRE trial. The agency stated that the acceptability of an NDA based on a single Phase 3 study would be considered on a case-by-case basis, taking into account the magnitude, consistency, and robustness of efficacy results, their generalizability to the US population, relevance to clinical practice, supportive Phase 2 findings, and an adequate safety database.

The FDA also acknowledged Acurx’s planned recurrent CDI study and indicated that successful results from this trial could provide additional supportive evidence for an NDA submission. However, the agency noted that if the Phase 3 study does not satisfy these expectations, a second Phase 3 trial, consistent with the agreement reached during the End-of-Phase 2 meeting in April 2024, would be recommended.

“We are very pleased with the guidance and support received from FDA for continued development of ibezapolstat toward a potential NDA,” said Robert J. DeLuccia, Executive Chairman of Acurx Pharmaceuticals.

IBZ-ASPIRE trial designed to support two indications

The international IBZ-ASPIRE study is designed as a randomized, non-inferiority Phase 3 trial with the primary efficacy analysis conducted in the modified intent-to-treat (mITT) population. Approximately 550 patients in the mITT population will be randomized in a 1:1 ratio to receive either ibezapolstat or the standard-of-care antibiotic vancomycin.

If the study demonstrates non-inferiority to vancomycin for clinical cure, additional statistical analyses will evaluate superiority for reducing CDI recurrence and superiority for clinical cure. According to the FDA, a successful outcome from the Phase 3 trial, supported by additional clinical evidence, could support indications for both the treatment of acute CDI and the reduction of disease recurrence.

PATHFINDER study to support recurrence indication

Alongside the pivotal Phase 3 program, Acurx has initiated start-up activities for the open-label IBZ-PATHFINDER pilot study in patients with multiply recurrent CDI. The study will enroll patients who have experienced at least three CDI episodes during the previous 12 months, with patient enrollment expected to begin within the next few months.

The company believes findings from PATHFINDER, together with positive IBZ-ASPIRE results, could provide supportive evidence for an NDA seeking approval for both acute CDI treatment and reduction of recurrence. Acurx also stated that it is prepared to initiate the international Phase 3 program, subject to securing the necessary funding.

Phase 2 findings support continued development

The completed Phase 2 clinical program (NCT04247542) consisted of an open-label Phase 2a study followed by a randomized, double-blind, active-controlled Phase 2b trial conducted across 28 US clinical sites. The studies evaluated clinical efficacy, pharmacokinetics, microbiome changes, and bile acid metabolism in patients with CDI.

According to Acurx, findings published in The Lancet Microbe demonstrated that ibezapolstat caused less disruption of the gut microbiome than vancomycin while maintaining favorable secondary bile acid profiles, findings that may contribute to reducing the risk of recurrent CDI.

Novel antibiotic targets C. difficile while preserving the microbiome

Ibezapolstat is an investigational oral Gram-Positive Selective Spectrum (GPSS®) antibiotic and the first member of a new class of DNA polymerase IIIC inhibitors. Unlike broad-spectrum antibiotics, it selectively targets C. difficile while largely preserving beneficial gut bacteria, including Firmicutes and Actinobacteria, helping maintain a healthier intestinal microbiome.

The investigational therapy has received FDA Qualified Infectious Disease Product (QIDP) designation and Fast Track designation, as well as Small and Medium-sized Enterprise (SME) designation from the European Medicines Agency.

Subject to funding and successful clinical development, Acurx plans to advance the IBZ-ASPIRE Phase 3 trial and continue discussions with the FDA regarding a potential NDA for ibezapolstat in the treatment of CDI and reduction of disease recurrence.

Reference

FDA Provides Further Regulatory Guidance to Acurx Pharmaceuticals for the Ibezapolstat Clinical Development Program, Including the Potential for a Single-Phase 3-Trial Registration Plan and a Trial Design to Support Both Treatment and Reduction of Recurrence of C. difficile Infection :: Acurx Pharmaceuticals, Inc. (ACXP)