Etrasimod, an investigational, oral selective sphingosine-1-phosphate (S1P)–receptor modulator, also improved endoscopic features of EoE, overall symptom severity, and dysphagia in some patients, researchers reported.
Dr. Evan S. Dellon
“These results support further investigation of etrasimod in EoE,” said Evan S. Dellon, MD, MPH, AGAF, of the University of North Carolina at Chapel Hill.
Dr. Dellon presented the results from the phase 2 study at the October 2023 annual scientific meeting of the American College of Gastroenterology in Vancouver, Canada.
VOYAGE Study
In the VOYAGE study, 108 adults were included, with about half female and an average EoE diagnosis for nearly 5 years.
The patients were randomized to once-daily doses of etrasimod 2 mg, etrasimod 1 mg, or placebo for 24 weeks, followed by a 28-week still-ongoing extension period investigating the efficacy and safety of daily oral etrasimod 1 mg and 2 mg, compared with placebo.
After 24 weeks of treatment, there was a 52.4% reduction in peak eosinophil count (PEC) in the group of patients who were given a 2-mg daily dose of etrasimod compared to placebo, Dr. Dellon said.
Among patients given a 1-mg daily dose of etrasimod, there was a 27.4% reduction in PEC.
Meanwhile, there was a 61% increase in PEC for people who were given placebo.
Etrasimod also bested placebo on secondary outcomes in the VOYAGE study, including:
- Comprehensive histologic severity and extent scores, with a change of -0.2 in both etrasimod groups (P < .0001), compared with a slight increase for the placebo group.
- Endoscopic features (EREFS), with a decline of 1.3 for the 2-mg–dose etrasimod group (P = .0303), compared with a slight decline for the placebo group. There was a decline of 1.0 in the 1-mg–dose etrasimod group, but this was not statistically significant.
Higher Dose Arm, Better Results
In the email exchange with GI & Hepatology News, Dr. Dellon said this appears to be “a dose-response where the 2-mg dose is needed to see more prominent response, but the EREFS response is in the right direction with the 1-mg dose.”
The study found a statistically significant decrease in only one segment of the trial participants, those who took the 2-mg dose and had a history of dilation, as measured by the Dysphagia Symptom Questionnaire (DSQ). In that group, there was a reported decrease of 21.6 points from baseline.
“The average scores at baseline are in the low 30s. The range for DSQ (which is a composite score of daily measurements over 14 days) is from 0 to 84,” Dr. Dellon wrote. “A score in the 30s over 2 weeks is quite symptomatic, so a decrease of 21.6 points is substantial.”
Dr. Dellon and co-authors said etrasimod appeared to be well tolerated with a safety profile consistent with use of the drug in patients with ulcerative colitis.
In treatment-emergent adverse events, elevation of liver transaminases was reported among 4 of 39 patients (10.3%) in the 1-mg etrasimod group and 3 of the 41 patients (7.3%) in the 2-mg etrasimod group, compared with none in the placebo group.
Bilirubin elevation was reported in 2 patients (5.1%) in the 1-mg etrasimod group and none in the 2-mg etrasimod or placebo groups.