64 - Persistent Improvement in Dysphagia Symptoms for 52 Weeks Following a Single Administration of EP-104GI in RESOLVE, an Ongoing Phase 1b/2 Trial in Eosinophilic Esophagitis (Late-Breaking Abstract)
Evan S. Dellon, MD, MPH, FACG1, Waqqas Afif, MD, MSC, FRCPC2, Nam Q. Nguyen, MD, PhD, FRACP3, Hin Hin Ko, MD, BSC(Pharm), FRCPC4, Albert J. Bredenoord, MD, PhD5, Vik Peck, BJ6, Andrew Dye, PhD6, Amanda Malone, PhD6, Mark M. Kowalski, MD, PhD71UNC School of Medicine, Chapel Hill, NC; 2McGill University Health Center, Montreal, PQ, Canada; 3Royal Adelaide Hospital, Adelaide, South Australia, Australia; 4GI Research Institute, Vancouver, BC, Canada; 5Amsterdam University Medical Center, Amsterdam, Noord-Holland, Netherlands; 6Eupraxia Pharmaceuticals, Victoria, BC, Canada; 7Eupraxia Pharmaceuticals, Seattle, WA Introduction: Patients with eosinophilic esophagitis (EoE) experience esophageal inflammation leading to tissue remodeling and potentially severe symptoms of dysphagia, pain and food impaction. The efficacy of topical corticosteroids used in the treatment of EoE may be limited by their transient contact within the esophagus.
In contrast, EP-104GI was designed as an injectable, long-acting submucosal fluticasone propionate formulation. RESOLVE (NCT05608681) is an ongoing Phase 1b/2, multicenter, open-label, dose-escalation trial evaluating the safety, tolerability, and efficacy of EP-104GI in adult participants with EoE. Herein, we report improvements in dysphagia among the first cohort to complete an extended follow-up period of 52 weeks after a single administration of EP-104GI as part of the ongoing RESOLVE trial. Methods: EP-104GI was injected as a single administration in the esophagus in escalating doses (number of sites x dose per site; n=3 participants per cohort). Participants were followed for up to 24 (4x1mg, 8x1mg, 8x2.5mg and 12x2.5mg) or 52 weeks (12x4mg and subsequent ongoing dose levels). Impact on dysphagia was assessed using the Straumann Dysphagia Index (SDI), evaluating the patient-reported frequency and intensity of dysphagia over a 7-day recall period.
Results: Prior, completed cohorts, with single administrations of up to 12x2.5mg of EP-104GI resulted in sustained mean improvements in eosinophil counts, histological scores and SDI score over 24 weeks. After 12, 24, 36 and 52 weeks respectively, following a single administration of 12x4mg EP-104GI, participants reported mean relative changes from baseline in SDI total score of -41%, -65%, -65% and -35% (mean absolute changes: -2.3, -3.7, -3.7 and -2). Changes from baseline in individual SDI subscales showed improvements in both frequency (-43%, -71%, -43%, -29%) and intensity (-40%, -60%, -80%, -40%) of dysphagia at week 12, 24, 36 and 52, respectively. At 52-week follow-up, no serious adverse events have been reported and EP-104GI has been well tolerated, without signs of adrenal insufficiency or oral and gastrointestinal candidiasis.. Discussion: This is the first report of persistent, clinically meaningful improvement in dysphagia over 52 weeks following a single administration of EP-104GI in participants with EoE. Overall, our results support the continued investigation of escalating dose levels of EP-104GI for the treatment of EoE in the ongoing RESOLVE trial.
