Announcement • Aug 05
Acurx Pharmaceuticals Receives FDA Guidance For Ibezapolstat Clinical Development Program And Initiates IBZ-PATHFINDER Trial
Acurx Pharmaceuticals has received FDA guidance in meeting minutes from a July 13, 2026 Type C Meeting to discuss ibezapolstat's (IBZ) Phase 3 clinical program, including the potential to submit an NDA (New Drug Application) based on a single Phase 3 trial and a clinical trial design intended to support indications for both treatment and reduction of recurrence of Clostridioides difficile infection (CDI). FDA stated that it is open to further discussion on the totality of evidence from the clinical development program at a pre-NDA meeting after completion of a single Phase 3 trial and any other clinical trials conducted prior to the pre-NDA meeting, particularly if the clinical efficacy results are robust. Additionally, the Agency agreed that a successful clinical outcome from a single IBZ-ASPIRE Phase 3 trial, supported by the open-label IBZ-PATHFINDER Phase 2 trial in multiply-recurrent CDI (rCDI) will allow NDA filing for both the acute treatment and the reduction of recurrence of CDI. Trial start-up activities for the IBZ-PATHFINDER ground-breaking clinical trial in patients with rCDI have been initiated with patient enrollment to begin in the next few months. Acurx is well positioned to commence its international Ph3 IBZ-ASPIRE trial, subject to funding availability. Acurx has previously been granted FDA QIDP and Fast-Track Designation and has received SME (Small and Medium-sized Enterprise) designation by the EMA. The Agency stated that it is open to further discussion at a Pre-NDA Meeting regarding 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 that Acurx may generate by that milestone. The Agency noted that determination of acceptability of one Phase 3 clinical trial for an NDA is made on a case-by-case basis, taking into consideration such factors as the magnitude, consistency, and overall robustness of the efficacy results; generalizability of the results to the US population; relevance of the results to US patient care and clinical practice guidelines; Phase 2 data; and an adequate safety database. The Agency acknowledged Acurx's planned clinical trial in recurrent CDI (rCDI) and noted the data from this rCDI trial, if successful, will support an NDA submission. If the IBZ-ASPIRE trial does not meet these criteria, then a second trial consistent with the agreement reached at the end of Phase 2 (EOP2) meeting on April 27, 2024, is recommended. The currently planned IBZ-ASPIRE trial is of non-inferiority design with the primary efficacy analysis in the Modified Intent-To-Treat (mITT) population. This will result in approximately 550 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard-of-care vancomycin. The Agency also agreed with the overall trial design and evaluation criteria and further agreed that the trial testing criteria, if successful, could support indications for both the acute treatment and the reduction of recurrence of CDI. In the event non-inferiority of ibezapolstat to vancomycin for Clinical Cure of CDI is demonstrated, further analyses will be conducted to test for superiority for reduction of recurrence and for clinical cure of CDI. Acurx previously announced that it is conducting a new clinical trial (IBZ-PATHFINDER) in patients with multiply recurrent C. difficile Infection (rCDI) while its program in the broader CDI patient population is ready to advance to Phase 3 international clinical trials (IBZ-ASPIRE), subject to receiving appropriate funding. This new IBZ-PATHFINDER clinical trial in rCDI involves an open-label pilot trial to gain experience with IBZ in patients with multiply-recurrent CDI with at least 3 episodes of CDI within the past 12 months. The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline and continue to test for anti-recurrence microbiome properties seen in the Phase 2a trial, including the treatment-related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism. Ibezapolstat is the Company's lead antibiotic candidate planning to advance to international Phase 3 clinical trials to treat patients with C. difficile infection. Ibezapolstat is a novel, orally administered antibiotic, being developed as a Gram-Positive Selective Spectrum (GPSS®) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome. In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI. Additionally, the Company has initiated start-up activities for a ground-breaking clinical trial in patients with rCDI with the first patient expected to enroll in the fourth quarter this year. This trial is a 20-patient, open-label pilot trial in patients with multiply-recurrent CDI with at least 3 episodes of CDI in the past year and will inform elements of a planned active-controlled, Phase 3 registration trial in the rCDI. Upon subsequent successful completion of a Ph3 pivotal rCDI trial, and per the operative FDA procedure, Acurx plans to request FDA approval for treatment and prevention of rCDI under the FDA's Limited Population Pathway for Antibacterial and Antifungal Drugs (Guidance for Industry, 2020). Successful trial outcome has the potential to shift the paradigm of treatment and prevention of rCDI from two agents to one.
