EFFICACY AND SAFETY OF THE SELECTIVE SPHINGOSINE 1-PHOSPHATE RECEPTOR MODULATOR, ETRASIMOD, IN ADULT PATIENTS WITH EOSINOPHILIC ESOPHAGITIS OVER 52 WEEKS IN THE PHASE 2 VOYAGE STUDY

Background: Etrasimod is an investigational, oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator in development to treat immune-mediated inflammatory disorders. Here, we report 52-week (wk) efficacy and safety data from the phase 2 VOYAGE trial in adults with active eosinophilic esophagitis (EoE).

Methods: VOYAGE (NCT04682639) included a 24-wk randomized, double-blind, placebo (PBO)-controlled treatment period, followed by a 28-wk extension. At Wk 24, patients (pts) continued on etrasimod 1 or 2 mg QD or were randomized from PBO to etrasimod 1 or 2 mg QD (data not shown) for 28 weeks (investigator and pts remained blinded). The efficacy analyses presented include data from PBO-controlled and extension treatment period outcomes at Wk 52 with focus on pts who received etrasimod in both periods (etrasimod 2 mg–2 mg and 1 mg–1 mg). Efficacy endpoints included percentage change from baseline (BL) (%CFB) in esophageal peak eosinophil count (PEC) at Wk 16 (primary endpoint), the proportion of pts who achieved PEC <15 and ≤6 eosinophils/high power field (eos/HPF), the CFB in EoE-Histology Scoring System (EoE-HSS) grade and stage scores, EoE-Endoscopic Reference Score (EREFS), Patient Global Impression of Severity (PGIS), and Dysphagia Symptom Questionnaire (DSQ; overall and by BL dilation history) at Wks 16, 24, and 52. Safety data are presented to Wk 52.

Results: As previously reported, 108 pts were randomized in the PBO-controlled period; 85 pts entered the extension period, with 30 and 31 maintaining etrasimod 2 and 1 mg QD, respectively (safety analysis set). Treatment with etrasimod 2 mg QD resulted in a 46.1% decrease from BL in PEC (PBO-adjusted) at Wk 16 (p=0.0103; Table 1) with the improvement maintained at Wks 24 and 52. Other histological and endoscopic endpoints, including eosophageal PEC <15 and ≤6 eos/HPF, EREFS, and EoE-HSS also showed statistically significant improvement at Wks 16 and 24, with improvements sustained at Wk 52 in pts who received etrasimod 2 mg QD for the full duration of the study (Table 1). Statistically significant reductions in PGIS in the overall population and DSQ in pts without BL dilation history who received etrasimod 2 mg QD were observed at Wk 24 (-0.48 and -11.95, respectively; p<0.05 for both parameters). PGIS and DSQ score improvements (overall population) were maintained to Wk 52 in pts who received etrasimod 1 or 2 mg QD. Etrasimod safety was consistent in both study periods and across dosages (Table 2).

Conclusion: Improvements in histological and endoscopic features of EoE at Wks 16 and 24, and improvements in symptoms (PGIS and DSQ in pts without dilation) at Wk 24 in pts who received etrasimod 2 or 1 mg QD were sustained at 52 wks. The etrasimod safety profile in pts with EoE appears consistent with that previously observed in other indications.