Acurx Enrolls First Patient in PATHFINDER Phase 2 Trial of Ibezapolstat in Multiply Recurrent C. difficile Infection
核心洞察
Acurx Pharmaceuticals has enrolled the first patient in PATHFINDER, a fully funded Phase 2 pilot trial of ibezapolstat in roughly 20 patients with multiply recurrent C. difficile infection.
PATHFINDER is an open-label, single-arm study in patients with at least three CDI episodes in the past 12 months, with 14 days of treatment and assessments through Week 24.
The company plans to use PATHFINDER data alongside a single Phase 3 ASPIRE trial to support an NDA for both acute treatment and reduction of CDI recurrence.
Acurx Pharmaceuticals has enrolled the first patient in PATHFINDER, a Phase 2 pilot trial of its lead antibiotic candidate ibezapolstat in patients with multiply recurrent Clostridioides difficile infection (搜索) (rCDI). The company announced the enrollment on Sept. 29, 2026.
PATHFINDER is a multicenter, open-label, single-arm Phase 2 study that will enroll approximately 20 patients who have experienced at least three episodes of CDI within the past 12 months. Participants receive ibezapolstat for 14 days and are assessed for Clinical Cure at Day 16, Sustained Clinical Cure at Day 42, rate of CDI recurrence through Week 24, and Extended Clinical Cure through Week 24. Acurx said the trial is fully funded.
Regulatory path toward a single Phase 3 trial
According to Acurx, PATHFINDER is intended to support filing of a U.S. New Drug Application based on a single Phase 3 trial. The company said that upon successful completion of PATHFINDER it plans to request FDA approval for the treatment and prevention of rCDI under the FDA's Limited Population Pathway for Antibacterial and Antifungal Drugs.
The regulatory groundwork was laid at a Type C Meeting with FDA held on July 13, 2026, which Acurx described as successful. In meeting minutes, the agency stated it is open to further discussion at a Pre-NDA Meeting about the possibility of submitting an NDA with only a single Phase 3 trial, depending on the totality of the clinical data plus any other supportive data generated by that milestone. FDA noted that acceptability of one Phase 3 trial for an NDA is determined case by case, taking into account the magnitude, consistency and overall robustness of efficacy results, generalizability to the U.S. population, relevance to U.S. patient care and clinical practice guidelines, Phase 2 data, and an adequate safety database.
FDA acknowledged Acurx's planned trial in recurrent CDI and noted that data from this rCDI trial, if successful, would support an NDA submission. If the ASPIRE trial does not meet these criteria, the agency recommends a second trial consistent with the agreement reached at the end-of-Phase 2 meeting on April 27, 2024.
ASPIRE Phase 3 design
The planned international IBZ-ASPIRE trial is of non-inferiority design with the primary efficacy analysis in the Modified Intent-To-Treat population, targeting approximately 550 subjects randomized 1:1 to ibezapolstat or standard-of-care vancomycin. FDA agreed with the overall trial design and evaluation criteria and agreed that the testing criteria, if successful, could support indications for both acute treatment and reduction of recurrence of CDI. If non-inferiority to vancomycin for Clinical Cure is demonstrated, further analyses will test for superiority for reduction of recurrence and for clinical cure.
Acurx said it is positioned to commence the ASPIRE trial, subject to funding availability, having alignment with both FDA and the European Medicines Agency on the Phase 3 program and the pathway to a U.S. NDA and an EU Marketing Authorisation Application. ASPIRE will be conducted when the company has sufficient resources from public or private partnerships to fund it.
Mechanism and prior data
Ibezapolstat is an orally administered, Gram-Positive Selective Spectrum antibacterial and the first of a new class of DNA polymerase IIIC (搜索) inhibitors under development by Acurx. Its spectrum of activity includes C. difficile but spares other Firmicutes and the Actinobacteria phyla, which the company says appears to contribute to maintenance of a healthy gut microbiome.
The completed Phase 2 program comprised a multicenter, open-label, single-arm Phase 2a segment followed by a double-blind, randomized, active-controlled, non-inferiority Phase 2b segment at 28 U.S. sites. That trial evaluated clinical efficacy in CDI, pharmacokinetics and microbiome changes from baseline, including treatment-related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism. Data were published in The Lancet in August 2025.
In the Phase 2b trial, ibezapolstat-treated patients showed lower concentrations of fecal primary bile acids and a higher ratio of secondary to primary bile acids than vancomycin-treated patients. Primary bile acids promote germination of C. difficile spores and increase the risk of recurrence, while secondary bile acids, produced by normal gut microbiota, do not induce sporulation and protect against recurrent disease. Because ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues, which may contribute to an anti-recurrence effect.
Disease burden and unmet need
C. difficile is one of the most common causes of healthcare-associated infections in U.S. hospitals and has been designated an urgent threat by the CDC. Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 30,000 deaths annually. Acurx said its internal estimates put annual U.S. incidence near 600,000 infections with a mortality rate of approximately 9.3%.
Recurrence rates for currently used CDI antibiotics are between 20% and 40% among approximately 150,000 patients treated, according to the company. In recent studies, rCDI incidence ranges from 4% to 19.5% following fidaxomicin and 17% to 27% following vancomycin; in patients with multiple prior episodes, recurrence after vancomycin reaches up to 40%. Acurx said the principal unmet medical need in this disease is prevention of recurrence. The estimated annual U.S. public health cost burden is approximately $5 billion, of which about $2.8 billion is attributable to recurrent CDI.
"PATHFINDER by itself in patients with multiply-recurrent CDI will inform elements of a planned active-controlled, Phase 3 registration trial in rCDI," the company stated. Acurx Executive Chairman Bob DeLuccia said the company believes ibezapolstat has the potential to be the first agent to demonstrate clinical success in both the treatment of CDI and the prevention of rCDI, potentially shifting the paradigm of treatment and prevention from two agents to one.
Ibezapolstat holds FDA Qualified Infectious Disease Product designation, granted in June 2018, and Fast Track designation, granted in 2019, and is eligible for incentives under the GAIN Act. The EMA has granted the company Small and Medium-sized Enterprise designation. Acurx's preclinical pipeline includes an oral candidate for acute bacterial skin and skin structure infections, with a development program for prophylaxis of inhaled anthrax planned in parallel.