P038 Ozanimod First-Dose Cardiac Effects in Patients with Moderately to Severely Active Ulcerative Colitis and...

Area of Science:

• Pharmacology
• Cardiology
• Immunology

Background:

• Ozanimod is an S1P receptor modulator approved for ulcerative colitis (UC) and multiple sclerosis (MS).
• A 7-day dose escalation regimen was implemented to mitigate first-dose cardiac effects observed in healthy participants.
• This analysis assessed cardiac contraindications and first-dose cardiac events in UC and MS clinical trials.

Purpose of the Study:

• To evaluate the number of patients excluded from ozanimod treatment due to cardiac contraindications.
• To assess the incidence of cardiac-related treatment-emergent adverse events (TEAEs) after the first ozanimod dose in UC and MS trials.
• To analyze cardiac events in patients with and without a history of cardiac disorders.

Main Methods:

• Pooled data from Phase 2/3 UC (Touchstone, True North) and Phase 3 MS (Radiance, Sunbeam) trials were analyzed.
• Patients with clinically relevant cardiac conditions or ECG disorders were excluded.
• Cardiac monitoring on Day 1 included vital signs and ECGs for at least 6 hours post-dosing.

Main Results:

• Low exclusion rates due to cardiac disorders: 1.2% in UC and 1.4% in MS.
• First-dose cardiac TEAEs were low: 0.2% in UC (1 asymptomatic bradycardia) and 0.6% in MS (11 events).
• No second- or third-degree AV block observed; heart rate decreased transiently and returned to baseline.

Conclusions:

• The incidence of exclusionary cardiac disorders in ozanimod trials for UC and MS was low.
• Most patients with a history of cardiac disorders tolerated the first dose of ozanimod without significant cardiac events.
• Cardiac events that occurred were manageable, supporting the safety profile of ozanimod with dose escalation.