S853 Long-term Safety of Ozanimod in Patients with Moderately to Severely Active Ulcerative Colitis (UC) and Relapsing Multiple Sclerosis (RMS) Studies

Abstract

Introduction: Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved in the US for the treatment of adults with moderately to severely active UC, and in adults with relapsing forms of multiple sclerosis (MS) and in the EU and other countries for the treatment of adults with relapsing-remitting MS. Here we report the safety of extended exposure to ozanimod HCl 1 mg/day from the UC and relapsing MS (RMS) clinical trials. Methods: Safety data were pooled from patients who received ozanimod 1 mg/day from all controlled and uncontrolled UC studies, including phase 2 and 3, and an ongoing, open-label extension (OLE) trial. As of September 30, 2020, safety data were available for 1158 UC patients with a mean ozanimod exposure of 22 months and a total of 2196.4 person-years (PY) exposure. RMS data were examined from DAYBREAK, an ongoing OLE trial that enrolled patients from 4 randomized phase 1, 2, or 3 parent trials; as of December 20, 2019, OLE data were available for 2494 RMS patients on ozanimod 1 mg/day for a mean of 35 months and a total exposure of 7161.0 PY. Results: Treatment-emergent adverse events (TEAEs) occurred in 70.8% and 81.8% of patients in the UC and RMS populations, respectively. Severe TEAEs occurred in 10.2% and 6.1%, and serious TEAEs in 14.0% and 9.5% of patients with UC and RMS, respectively. TEAEs led to treatment discontinuation in 8.0% of patients in the UC studies and 2.2% of patients in the RMS study. The most frequently reported TEAEs in the UC studies were lymphopenia (10.3%), nasopharyngitis (7.5%), and anemia (7.9%); exposure-adjusted incidence rates (IRs) per 100 PY were 5.84, 4.20, and 4.39, respectively. The most frequently reported TEAEs in the RMS study were nasopharyngitis (17.9%), headache (14.0%), upper respiratory tract infection (9.9%), and lymphopenia (9.6%); exposure-adjusted IRs per 100 PY were 6.99, 5.30, 3.67, and 3.61, respectively. IRs for infections (any) were 21.48 and 26.49, and IRs for serious infections were 1.29 and 0.72 in the UC and RMS datasets, respectively. IRs per 100 PY for TEAEs of special interest (herpes zoster, bradycardia, and macular edema) were low (Table). Increased alanine aminotransferase to >5x the upper limit of normal occurred in 2.1% of UC patients and 0.7% of MS patients. Conclusion: Long-term exposure to ozanimod 1 mg/day in patients with moderately to severely active UC and in patients with RMS was manageable, with low rates of safety events related to S1P modulators.Table 1.: TEAEs of special interest (based on prior associations with S1P receptor modulation).