Acurx Announces Positive Opinion from EMA on Pediatric Investigation Plan for Ibezapolstat Use in Children with C. difficile Infection

STATEN ISLAND, N.Y.,Sept. 30, 2025/PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ:ACXP) ("Acurx" or the "Company") is a late-stage biopharmaceutical company developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections announced receipt of a favorable opinion from the PDCO of the EMA on Acurx's Pediatric Investigation Plan (PIP) for ibezapolstat use in children withC. difficileinfection (CDI).

C. difficile is the most important infectious cause of antibiotic-associated diarrhea worldwide and a leading cause of healthcare-associated infection in the United States. The incidence of CDI in children has increased, with 20,000 cases now reported annually. CDI in children is more commonly community-associated, accounting for three-quarters of all cases. A wide spectrum of disease severity ranging from asymptomatic carriage to severe diarrhea can occur, varying by age. Fulminant disease, although rare in children, is associated with high morbidity and even fatality. Similar to disease in adults, recurrence of CDI in children is common, affecting 20% to 30% of incident cases. Recent advancements in understanding of emerging epidemiologic trends and management of CDI unique to children are being realized. Despite encouraging therapeutic advancements, there remains a pressing need to optimize CDI therapy in children, particularly as it pertains to severe and recurrent disease.*

Acurx's Executive Chairman, Bob DeLuccia, stated: We're very pleased to have received this positive EMA opinion as part of our EMA regulatory pathway, since there is a significant unmet need for an innovative antibiotic to treat children suffering from CDI. Our pediatric clinical trial program is designed to demonstrate that ibezapolstat will be a safe and effective treatment that could represent a transformative advance to achieve CDI cure, reduce recurrences, and preserve the gut microbiome in this vulnerable patient population. Importantly, this could lead to reduction of the overall antimicrobial exposure in children with CDI." He added: "Additionally, ibezapolstat would be eligible to apply for an additional one year of marketing exclusivity in Europe on top of the 10 years exclusivity period to be granted for a successful MAA for a new class of antibiotic."

* Adapted from: Shirley DA, Tornel W, Warren CA, Moonah S. Clostridioides difficile Infection in Children: Recent Updates on Epidemiology, Diagnosis, Therapy. Pediatrics. 2023 Sep 1;152(3):e2023062307. doi: 10.1542/peds.2023-062307. PMID: 37560802; PMCID:PMC10471512.

Acurx previously announced that it had received positive regulatory guidance from the EMA during its Scientific Advice Procedure which confirmed that the clinical, non-clinical and CMC (Chemistry Manufacturing and Controls) information package submitted to EMA supports advancement of the ibezapolstat Phase 3 program and if the Phase 3 program is successful, supports the submission of a Marketing Authorization Application (MAA) for regulatory approval in Europe. The information package submitted to EMA by the Company to which agreement has been reached with EMA included details on Acurx's two planned international Phase 3 clinical trials, 1:1 randomized (designed as non-inferiority vs vancomycin), primary and secondary endpoints, sample size, statistical analysis plan and the overall registration safety database. With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence our international Phase 3 registration program.

The primary efficacy analysis will be performed using a Modified Intent-To-Treat (mITT) population. This will result in an estimated 450 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard- of-care vancomycin, enrolled into the initial Phase 3 trial. The trial design not only allows determination of ibezapolstat's ability to achieve Clinical Cure of CDI as measured 2 days after 10 days of oral treatment but also includes assessment of ibezapolstat's potential effect on reduction of CDI recurrence in the target population. In the event non-inferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority.

In the Phase 2b trial segment, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. In this Phase 2b trial segment, 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population experienced Clinical Cure (CC) and all 15 of 15 (100%) remained free of C. difficile infection (CDI) recurrence through one month after EOT.

When Phase 2b results are combined with Phase 2a results, the Clinical Cure rate in patients with CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a in the Modified Intent to Treat Population, plus 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who experienced Clinical Cure during treatment with ibezapolstat. Notably, in the combined Phase 2 trial, 100% (25 of 25) ibezapolstat-treated patients) who had Clinical Cure at EOT) (End of Treatment) remained cured through one month after EOT, as compared to 86% (12 of 14) for the vancomycin patient group. Ibezapolstat was well-tolerated, with no serious adverse events assessed by the blinded investigator to be drug- related. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of 96%, Sustained Clinical Cure Rate of 100% and the historical vancomycin Clinical Cure Rate range of 70% to 92% and a Sustained Clinical Cure historical range of 42% to 74%, we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials, in accordance with the applicable FDA Guidance for Industry (October 2022), with favorable differentiation in both Clinical Cure and Sustained Clinical Cure.

In the Phase 2 clinical trial (both trial segments), the Company also evaluated pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin. The company also reported positive extended clinical cure (ECC) data for ibezapolstat (IBZ), its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. This exploratory endpoint showed that 5 of 5 IBZ patients followed for up to three months following Clinical Cure experienced no recurrence of infection. Furthermore, ibezapolstat-treated patients showed lower concentrations of fecal primary bile acids, and higher beneficial ratio of secondary to primary bile acids than vancomycin-treated patients.

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 designatedC. difficileas an urgent threat highlighting the need for new antibiotics to treat CDI.