Eupraxia Pharmaceuticals Inc. announced positive clinical data from the fifth cohort of its RESOLVE Phase 1b/2a trial, evaluating EP-104GI for the treatment of eosinophilic esophagitis (EoE). The data reveal promising efficacy and safety outcomes, suggesting a potential breakthrough in EoE treatment.
The RESOLVE trial is a multicenter, open-label, dose-escalation study assessing the safety, tolerability, pharmacokinetics, and efficacy of EP-104GI in adults with histologically confirmed active EoE. EP-104GI is administered via injections into the esophageal wall, allowing for targeted drug delivery.
Key Findings from Cohort 5
The fifth cohort received 12 injections of 4 mg EP-104GI (total dose of 48 mg). Key results include:
- Histological Remission: One patient achieved complete histological remission at 12 weeks, defined as fewer than six eosinophils per high-powered field on esophageal biopsy.
- Symptom Improvement: All three patients showed lower Straumann Dysphagia Index (SDI) scores post-administration, with peak reductions up to 3 points (50% from baseline). The mean SDI reduction was 41% or 2.3 points at 12 weeks.
- Histology Score Reduction: Eosinophilic Esophagitis Histology Scoring System (EoEHSS) scores showed the largest percent reduction of any cohort to date at 12 weeks, with a mean 54% reduction in Composite Stage and Grade scores.
- Eosinophil Count Reduction: The mean reduction in Peak Eosinophil Counts (PEC) was 83% at 12 weeks, based on data from four biopsy sites, consistent with FDA guidance.
Data from Cohort 4
Data from the fourth cohort, which received 12 injections of 2.5 mg EP-104GI (total dose of 30 mg), showed continued improvement in SDI scores out to 24 weeks, with an average four-point reduction. EoEHSS Composite Stage and Composite Grade scores were both lower than baseline at 12 weeks, showing an average reduction of 39% and 37%, respectively. The mean reduction in PEC was 67% at 12 weeks.
Safety Profile
Plasma fluticasone levels remained predictable and well below published levels of daily fluticasone asthma treatments. No serious adverse events, such as candidiasis, adrenal suppression, or glucose derangement, have been reported in any of the five cohorts to date.
Implications and Future Directions
"As the RESOLVE trial advances, we are observing increasingly positive data on efficacy and safety outcomes," said Dr. James Helliwell, Chief Executive Officer of Eupraxia. "Notably, higher dosing levels are yielding improved patient responses...all without reaching a maximum tolerated dose thus far."
Cohort 6 is now fully enrolled and dosed, with 12-week data anticipated in Q1 2025. These findings suggest that EP-104GI could offer a significant advancement in the treatment of EoE, addressing a substantial unmet medical need. EoE affects over 450,000 people in the United States and is characterized by white blood cells migrating into the esophagus, causing pain and difficulty swallowing.
