Acurx Receives EMA Approval for Pediatric Investigation Plan for Ibezapolstat in C. difficile Infection
Key Insights
The European Medicines Agency (search)'s Paediatric Committee issued a positive opinion on Acurx's Pediatric Investigation Plan for ibezapolstat use in children with C. difficile infection (search).
This regulatory milestone fulfills EMA requirements for initiating Phase 3 clinical trials in the European Union and positions the company to begin international trials.
Ibezapolstat demonstrated a 96% clinical cure rate and 100% sustained clinical cure rate in Phase 2 trials, significantly outperforming historical vancomycin outcomes.
Acurx Pharmaceuticals has received a favorable opinion from the European Medicines Agency (search)'s Paediatric Committee (PDCO) on its Pediatric Investigation Plan (PIP) for ibezapolstat, marking a crucial regulatory milestone for the company's novel antibiotic candidate targeting C. difficile infection (search) (CDI) in children.
The positive opinion fulfills the EMA's requirement for PIP approval before initiating Phase 3 clinical trials in the European Union. This development, combined with previous regulatory alignment from both the EMA and FDA on the adult clinical trial program, positions Acurx to commence international Phase 3 registration trials for its lead antibiotic candidate.
Addressing Critical Pediatric Need
C. difficile represents the most important infectious cause of antibiotic-associated diarrhea (search) worldwide and a leading cause of healthcare-associated infection in the United States. The incidence of CDI in children has increased significantly, with 20,000 cases now reported annually. Pediatric CDI is predominantly community-associated, accounting for three-quarters of all cases, and presents unique challenges compared to adult disease.
"There is a significant unmet need for an innovative antibiotic to treat children suffering from CDI," stated Bob DeLuccia, Acurx's Executive Chairman. "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."
The disease spectrum in children ranges from asymptomatic carriage to severe diarrhea, with fulminant disease, though rare, associated with high morbidity and mortality. Recurrence affects 20% to 30% of incident cases, similar to adult populations, highlighting the need for more effective therapeutic options.
Phase 3 Trial Design and Regulatory Pathway
The upcoming Phase 3 program will utilize a Modified Intent-To-Treat (mITT) population with an estimated 450 subjects randomized 1:1 to either ibezapolstat or standard-of-care vancomycin. The trial design will assess ibezapolstat's ability to achieve clinical cure of CDI measured 2 days after 10 days of oral treatment, while also evaluating its potential effect on reducing CDI recurrence.
If non-inferiority to vancomycin is demonstrated, further analysis will be conducted to test for superiority. The company has received mutually consistent feedback from both EMA and FDA, providing a clear regulatory pathway for both European Marketing Authorization Application (MAA) and U.S. New Drug Application (NDA) submissions.
Promising Phase 2 Results
Ibezapolstat demonstrated compelling efficacy in its completed Phase 2 clinical trial program. The combined Phase 2a and 2b results showed a clinical cure rate of 96% (25 out of 26 patients), with 100% of patients who achieved clinical cure at end of treatment remaining cured through one month after treatment completion.
In comparison, the vancomycin control group achieved an 86% sustained clinical cure rate (12 of 14 patients). These results compare favorably to historical vancomycin clinical cure rates of 70% to 92% and sustained clinical cure rates of 42% to 74%.
The Phase 2b segment specifically enrolled 32 patients randomized 1:1 to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg every 6 hours for 10 days. In the per protocol population, 15 out of 16 (94%) patients treated with ibezapolstat experienced clinical cure, with all 15 remaining free of CDI recurrence through one month after treatment.
Unique Mechanism and Microbiome Preservation
Ibezapolstat represents the first of a new class of DNA polymerase IIIC (search) inhibitors, functioning as a Gram-Positive Selective Spectrum (GPSS®) antibacterial. Its unique spectrum of activity includes C. difficile but spares other Firmicutes and important Actinobacteria phyla, contributing to maintenance of a healthy gut microbiome.
Phase 2 data demonstrated complete eradication of colonic C. difficile by day three of treatment, along with observed overgrowth of healthy gut microbiota, specifically Actinobacteria and Firmicute phyla species. Importantly, emerging data show increased concentration of secondary bile acids during and following ibezapolstat therapy, which correlates with colonization resistance against C. difficile.
The favorable increase in the ratio of secondary-to-primary bile acids suggests ibezapolstat may reduce the likelihood of CDI recurrence compared to vancomycin. In the Phase 2b trial, ibezapolstat-treated patients showed lower concentrations of fecal primary bile acids and higher beneficial ratios of secondary to primary bile acids than vancomycin-treated patients.
Regulatory Designations and Market Exclusivity
Ibezapolstat has received several important regulatory designations that support its development pathway. The FDA designated it as a Qualified Infectious Disease Product (QIDP) in June 2018 and granted Fast Track designation in 2019 for CDI treatment. The EMA has provided Small and Medium-sized Enterprise (SME) designation to Acurx.
Upon successful MAA approval in Europe, ibezapolstat would be eligible for an additional one year of marketing exclusivity on top of the standard 10-year exclusivity period granted for new antibiotic classes, providing enhanced commercial protection for this novel therapeutic approach.
The CDC has designated C. difficile as an urgent threat, emphasizing the critical need for new antibiotics to treat CDI. Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S., associated with approximately 20,000 deaths annually, with recurrence rates for currently used antibiotics ranging between 20% and 40% among treated patients.