Acurx Receives Positive FDA Guidance for Ibezapolstat Phase 3 Program in C. difficile Infection

FDA Supports Continued Development of Ibezapolstat

Acurx Pharmaceuticals has announced a positive outcome from its recent Type C meeting with the US Food and Drug Administration (FDA), providing important guidance for the Phase 3 development of its lead antibiotic candidate, ibezapolstat.

The meeting focused on the company's Phase 3 clinical program and the planned New Drug Application (NDA) for ibezapolstat, which is being developed to treat Clostridioides difficile infection (CDI).

According to Acurx, the FDA indicated that it is willing to discuss a potential NDA submission based on a single successful Phase 3 clinical trial, provided the overall clinical evidence is strong enough.

Single Phase 3 Trial Could Support NDA Filing

The FDA explained that the possibility of approving an NDA based on one Phase 3 study will depend on the total clinical evidence available at the time of the pre-NDA meeting.

The agency will review several factors before making that decision, including:

• Strength and consistency of the efficacy results.
• Safety data collected throughout development.
• Relevance of the study results to patients in the United States.
• Phase 2 clinical data.
• Any additional supportive clinical evidence.

If the Phase 3 results are considered robust, the FDA is open to discussing approval based on one pivotal study instead of requiring two.

FDA Supports Two Treatment Indications

The agency also agreed that a successful outcome from the planned IBZ-ASPIRE Phase 3 study, together with supportive results from the IBZ-PATHFINDER study, could support approval for two indications.

These include:

• Treatment of acute Clostridioides difficile infection.
• Reduction of recurrence after treatment.

This guidance could simplify the clinical development pathway if the planned studies meet their objectives.

Phase 3 Trial Ready to Begin

Acurx stated that it is well positioned to begin its international Phase 3 IBZ-ASPIRE study once funding becomes available.

The trial has been designed as a non-inferiority study comparing ibezapolstat with the current standard treatment, vancomycin.

Approximately 550 patients in the modified intent-to-treat population will be enrolled and randomized equally between the two treatment groups.

The primary endpoint will evaluate clinical cure of CDI.

If non-inferiority is successfully demonstrated, additional analyses will test whether ibezapolstat is superior in reducing disease recurrence and improving overall clinical cure.

New Trial Will Focus on Recurrent Infection

Alongside the main Phase 3 study, Acurx has already started trial preparation activities for the IBZ-PATHFINDER study.

Patient enrollment is expected to begin within the next few months.

The study will evaluate ibezapolstat in patients with multiply recurrent Clostridioides difficile infection who have experienced at least three episodes during the previous year.

The open-label Phase 2 trial is expected to provide additional clinical data that could strengthen the planned NDA submission.

Company Welcomes FDA Feedback

Robert J. DeLuccia, Executive Chairman of Acurx Pharmaceuticals, said the company is pleased with the FDA's guidance and continued support for the development program.

He noted that if the IBZ-ASPIRE study successfully meets its endpoints, the company believes approval for both treatment of active infection and prevention of recurrence may be possible using data from a single Phase 3 study, supported by the recurrent infection trial.

Earlier Clinical Results Support Advancement

The current Phase 3 program is built on encouraging findings from the completed Phase 2 clinical trial.

The Phase 2 program included both an open-label Phase 2a study and a randomized, active-controlled Phase 2b study conducted across 28 clinical sites in the United States.

Researchers evaluated:

• Clinical cure rates.
• Drug safety.
• Pharmacokinetics.
• Changes in the gut microbiome.
• Bile acid metabolism.

The study also examined whether ibezapolstat could preserve healthy gut bacteria while reducing the likelihood of disease recurrence.

Results from the Phase 2 program were published in The Lancet in 2025.

How Ibezapolstat Works

Ibezapolstat is an investigational oral antibiotic designed specifically to treat Clostridioides difficile infection.

Unlike many broad-spectrum antibiotics, ibezapolstat belongs to a new class of Gram-Positive Selective Spectrum (GPSS®) antibiotics.

The medicine works by blocking bacterial DNA polymerase IIIC, an enzyme required for DNA replication in Gram-positive bacteria.

Its selective activity allows it to target C. difficile while preserving much of the healthy gut microbiome.

Researchers believe maintaining healthy gut bacteria may help reduce the risk of recurrent infections.

Fast Track and QIDP Designations Already Granted

The FDA has previously granted ibezapolstat two important regulatory designations.

These include:

• Qualified Infectious Disease Product (QIDP) designation.
• Fast Track designation.

In Europe, the European Medicines Agency has also granted Small and Medium-sized Enterprise (SME) designation to Acurx.

These designations are intended to support the development of innovative therapies for serious infectious diseases with limited treatment options.

Why New Treatments for CDI Are Needed

Clostridioides difficile infection remains one of the most common healthcare-associated infections.

The disease affects hundreds of thousands of patients every year in the United States and is responsible for significant illness, hospitalizations, and deaths.

One of the biggest challenges is recurrence.

Current treatments can leave patients at risk of repeated infections, with recurrence rates ranging from approximately 20% to 40%.

Patients who have already experienced multiple episodes may face recurrence rates approaching 40% or even higher.

Because of this, preventing recurrence remains one of the largest unmet needs in CDI treatment.

Acurx hopes that ibezapolstat's ability to preserve the gut microbiome while treating infection may offer a new approach for both treating active disease and lowering the chance of future recurrences.