EP-104GI Phase 1b/2a Signal: Durable Symptom Control Without Histological Proof Creates Regulatory Gap

Eupraxia Reports Positive Symptom Data for EP-104GI in EoE

Eupraxia Pharmaceuticals announced positive results from a new analysis of its Phase 1b/2a RESOLVE study for EP-104GI in Eosinophilic Esophagitis (EoE) patients. The analysis, which included new data on odynophagia (painful swallowing), demonstrated significant and durable reductions in both odynophagia and dysphagia (difficulty swallowing) severity. Patients treated with EP-104GI showed a decrease in moderate to severe symptoms, with no patients reporting severe odynophagia or dysphagia at 24 and 52 weeks post-treatment. The drug continued to be well tolerated, with no reported treatment-emergent or procedure-related Serious Adverse Events across over 130 patients.

• The analysis of Cohorts 7-9 showed a substantial reduction in odynophagia severity. The proportion of patients experiencing moderate to severe odynophagia decreased from 62% at baseline to 25% at 24 and 52 weeks post-treatment. Notably, severe odynophagia, reported by 23% of patients at baseline, was completely eliminated by the 24 and 52-week timepoints.
• Similar positive trends were observed for dysphagia. The number of patients experiencing moderate to severe dysphagia in Cohorts 7-9 was reduced from 77% at baseline to 25% at 24 and 52 weeks post-treatment. Furthermore, the 31% of patients who had severe dysphagia at baseline reported no severe dysphagia at the 24 and 52-week follow-ups.
• EP-104GI demonstrated a strong safety profile, with over 130 patients treated across more than 2,000 injection sites in the RESOLVE trial without any reported treatment-emergent or procedure-related Serious Adverse Events. The observed improvements in both odynophagia and dysphagia symptoms showed durability, lasting out to 52 weeks post-treatment.

EP-104GI Delivers Durable Symptom Relief and Strong Safety in EoE

Recent clinical studies in eosinophilic esophagitis (EoE) have evaluated both biologic and corticosteroid-based interventions across a range of histologic, symptomatic, and endoscopic endpoints. The evidence base spans short-term induction trials and long-term maintenance studies, providing a comprehensive view of treatment durability and tolerability.

• LIBERTY EoE TREET Trial (NCT03633617) — Dupilumab 300 mg weekly: Demonstrated improvements in histologic, symptomatic, and endoscopic endpoints at Week 24, sustained through Week 52, as measured by peak intraepithelial eosinophil count ≤6 eos/HPF and Dysphagia Symptom Questionnaire (DSQ) score. Efficacy was consistent regardless of prior swallowed corticosteroid use. The agent was well tolerated across the study population.

• DUPEOETALY Study — Dupilumab (72-week treatment): Showed progressive, duration-dependent improvements across all endpoints; by Week 72, 98.3% of patients achieved composite remission criteria (DSQ ≤5, eos ≤15/HPF, EREFS ≤2). DSQ scores declined from 22.14 ± 26.63 to 0.21 ± 2.30, and eos/HPF fell from 36.80 ± 31.75 to 0.06 ± 0.46. Adverse events were minimal, decreasing from 3.8% at Week 12 to 0% at Week 60.

• Budesonide Oral Suspension (BOS) Phase 2 Trial (NCT01642212) — BOS 2 mg twice daily for 12 weeks: In adolescent and young adult patients, BOS produced a significantly greater reduction in DSQ score vs. placebo (−14.3 vs. −7.5; P = .0096), histologic response rate (39% vs. 3%; P < .0001), and endoscopic severity score change (−3.8 vs. +0.4; P < .0001). Mean peak eosinophil counts declined from 156 to 39/HPF. Adverse event profiles were comparable between active and placebo arms.

• Long-Term BOS Study (SHP621-303) — BOS 2.0 mg twice daily for 4 years: At Month 48, 50.0–58.3% of patients maintained histologic response, and the initial EREFS reduction of −3.6 was sustained. Treatment-emergent adverse events (TEAEs) occurred in 76.3% of patients but were predominantly mild-to-moderate and unrelated to study drug; BOS-related TEAEs included abnormal ACTH stimulation test results (8.4%), adrenal insufficiency (2.3%), and esophageal candidiasis (3.1%), with most resolving over time.

• OVB vs. Fluticasone MDI Trial (NCT02019758) — Oral viscous budesonide (1 mg/4 mL) twice daily vs. fluticasone MDI (880 µg) twice daily for 8 weeks: Both formulations produced comparable and significant reductions in esophageal eosinophil counts, dysphagia, and endoscopic features, with no statistically significant between-group differences in post-treatment eos/HPF (15 vs. 21; P = .31), histologic response (71% vs. 64%; P = .38), or DSQ scores (5 vs. 4; P = .70). Esophageal candidiasis rates were similar at 12% (OVB) and 16% (MDI).

Unpacking RESOLVE: EP-104GI's Novel Local Delivery Approach in EoE

The landscape of advanced therapeutics in eosinophilic esophagitis (EoE) is characterized by key Phase 3 trials investigating targeted monoclonal antibodies, specifically benralizumab and dupilumab. In the MESSINA trial, a multicenter, double-blind, randomized, placebo-controlled Phase 3 study, 211 patients aged 12 to 65 with symptomatic and histologically active EoE were randomized in a 1:1 ratio to receive either subcutaneous benralizumab at 30 mg (n=104) or placebo (n=107) every 4 weeks. At week 24, the co-primary endpoints evaluated were histologic response (defined as ≤6 eosinophils per high-power field [eos/hpf]) and the change from baseline in the Dysphagia Symptom Questionnaire (DSQ) score. While benralizumab demonstrated a robust histologic response of 87.4% compared to 6.5% for placebo (a difference of 80.8 percentage points; 95% CI: 72.9 to 88.8; P<0.001), the change in DSQ score did not achieve statistical significance, with a least-squares mean difference of 3.0 points between groups (95% CI: -1.4 to 7.4; P=0.18). Safety profiles were comparable, with adverse events reported in 64.1% of the benralizumab group and 61.7% of the placebo group, and no discontinuations due to adverse events. Parallel to this, the Phase 3 R668-EE-1774 trial assessed the efficacy and safety of dupilumab over 24 weeks in 239 adults and adolescents with EoE (median age of 24 years, range 12–68 years). Key endpoints in this trial focused on patient-reported outcomes, utilizing the Eosinophilic Esophagitis Symptom Questionnaire (EoE-SQ) frequency and severity scores, the Patient Global Impression of Severity (PGIS), and the Patient Global Impression of Change, establishing meaningful clinical change thresholds as a minimum 3.7-point reduction in the EoE-SQ frequency score and a minimum 5.3-point reduction in the EoE-SQ severity score.

Complementing these registrational trials, prospective and retrospective real-world studies have helped define critical histological cutpoints and real-world treatment outcomes in EoE management. A prospective cohort study conducted at the University of North Carolina from 2009 through 2014 tracked 62 consecutive adult patients undergoing outpatient esophagogastroduodenoscopy through 8 weeks of standard treatment. Utilizing symptom response (visual analogue scale), endoscopic response (endoscopic severity score [ESS]), and histologic response as endpoints, the study showed that mean eosinophil counts fell from 124 eos/hpf at diagnosis to 35 eos/hpf post-treatment, yielding a 47% symptom response rate (29 patients) and a 55% endoscopic response rate (34 patients). Crucially, the study identified specific histological cutpoints: 8 eos/hpf best predicted symptom response, 15 eos/hpf best predicted endoscopic response, and 5 eos/hpf best predicted combined symptom and endoscopic responses. Additionally, a retrospective serial case review from Massachusetts General Hospital starting in 2007 analyzed 100 predominantly pediatric EoE cases, defining histological remission as a peak esophageal eosinophil count of <10/hpf. Among 97 patients undergoing initial treatment, dietary therapy achieved a 67% response rate (54 of 81) and topical glucocorticoids achieved a 56% response rate (9 of 16), while second-line rescue treatment succeeded in 54% of patients (13 of 24) who failed initial therapy. Overall response rates across this cohort reached 65% with initial treatment, 78% with rescue treatment, and 80% with multiple treatments under intent-to-treat analysis, rising to 93% (78 of 84) in the per-protocol analysis.

Addressing Persistent Challenges and Unmet Needs in Eosinophilic Esophagitis

Despite meaningful therapeutic advances in eosinophilic esophagitis (EoE), critical gaps remain in disease management across both pediatric and adult populations. Durability of response, fibrosis monitoring, and the management of refractory disease continue to represent significant clinical challenges that current treatment paradigms do not fully address.

• Pediatric populations, including very young patients: The January 2024 expansion of dupilumab approval to patients as young as 1 year of age (weighing ≥15 kg) reflects growing recognition of the unmet need for approved therapies in younger children. Case reports of infants requiring triple pharmacological therapy (dupilumab, PPI, and swallowed topical corticosteroids) for histological disease control underscore that management in very young patients remains particularly complex, with current guidelines providing limited guidance on combined pharmacological approaches.

• Refractory and difficult-to-manage disease: Patients with inadequate or unsustained responses to standard therapies represent a substantial unmet need. Among adult EoE patients who initially respond to corticosteroid therapy, 61% experienced histologic loss of response over time — with 50% losing response by 18.5 months and 75% by 29.6 months — highlighting an urgent requirement for more durable treatment options.

• Long-term fibrosis prevention and disease monitoring: The degree of inflammation control required to prevent stricture formation remains undefined. Symptom burden does not reliably correlate with underlying disease activity, and current monitoring approaches inconsistently evaluate fibrosis. Transmural rather than purely mucosal assessment of esophageal fibrosis and stricture formation has been identified as essential for accurately tracking disease trajectory.

• Optimisation of novel and emerging therapeutics: Biologics targeting key cytokines — including IL-4, IL-5, and IL-13 — offer promising avenues for improved disease control, yet long-term studies evaluating how agents such as dupilumab may alter the natural history of EoE are still awaited. Appropriate drug positioning and long-term treatment exit strategies remain to be defined.