Introduction
Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved for the treatment of moderately to severely active ulcerative colitis (UC) and for the treatment of relapsing multiple sclerosis (RMS). Ozanimod is a first-in-class S1P receptor modulator approved for UC, and one of several S1P receptor modulators used for the treatment of RMS. Ozanimod has been extensively studied in RMS with large patient populations and long exposure times, which can provide more insight into the safety profile of ozanimod in UC.
Aims & Methods
This analysis evaluated the tolerability and safety of long-term ozanimod 0.92 mg/day treatment from clinical trial data in adults with moderately to severely active UC and from clinical trial data in adults with RMS. The UC population included patients pooled from phase 2 (NCT01647516), phase 3 (NCT02435992), and respective open-label extension (OLE; NCT02531126) trials through January 10, 2022. The RMS population included patients treated with ozanimod 0.92 mg in DAYBREAK (NCT02576717; October 16, 2015–February 1, 2022), an ongoing OLE trial of patients from phase 1‒3 ozanimod studies. Safety outcomes included treatment-emergent adverse events (TEAEs) and TEAEs of special interest based on association with S1P modulation. Exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY) were calculated to adjust for time on study.
Results
Mean (SD) ozanimod exposure in 1158 patients with UC was 28.4 (23.3) months (2714.9 total PY exposure); ozanimod exposure in 2494 patients with RMS was 56.4 (15.9) months (11,732.2 PY; UC and MS combined: 14,447.1 PY). TEAEs occurred in 74.6% of UC and 88.2% of RMS patients. Serious TEAEs were reported in 17.3% of UC and 14.1% of RMS patients, and TEAEs leading to ozanimod discontinuation in 9.3% and 3.6%, respectively. The most common TEAEs were lymphopenia (12.3%; EAIR 5.6/100 PY), anemia (8.4%; EAIR 3.7/100 PY), lymphocyte count decreased (7.9%; EAIR 3.5/100 PY), and nasopharyngitis (7.9%; EAIR 3.5/100 PY) in patients with UC, and nasopharyngitis (20.6%; EAIR 5.1/100 PY), headache (16.9%; EAIR 4.0/100 PY), and upper respiratory infection (11.9%; EAIR 2.7/100 PY) in patients with RMS. In UC and MS, respectively, EAIR/100 PY were 20.2 and 22.9 for any infection, 1.6 and 0.8 for serious infection, 1.2 and 1.4 for opportunistic infection, and 0.6 and 0.3 for malignancy. Alanine aminotransferase levels ≥5 times the upper limit of normal occurred in 2.3% and 0.8% of UC and RMS patients, respectively.
Conclusion
Long-term ozanimod 0.92 mg/day was generally well tolerated and safe for most patients with moderately to severely active UC or RMS.
Disclosure
SD: received honoraria as a speaker, consultant, and/or advisory board member from AbbVie, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, and Vifor.
BACC: received personal compensation for consulting for Alexion, Atara, Autobahn Therapeutics, Avotres, Biogen, EMD Serono, Gossamer Bio, Horizon Therapeutics, Neuron23, Novartis, Sanofi, TG Therapeutics, and Therini Bio; and received research support from Genentech.
DCW: received research honoraria as a speaker, consultant, and/or advisory board member from AbbVie, Arena, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Pfizer, and Takeda.
OA: received honoraria as a speaker from Janssen, Pfizer, and Takeda.
LC, AP, JKS, CYC, JVR, and DS: employees and/or shareholders of Bristol Myers Squibb.
FDL: participated in consulting agreements, advisory boards, and/or data and safety monitoring boards with Acorda, Actelion, Apitope, Atara, Biogen, BrainStorm Cell Therapeutics, EMD Serono, GW Pharmaceuticals, Immunic, Innate Immunotherapeutics, Jazz Pharmaceuticals, Mapi Pharma, MedDay, MedImmune/Viela Bio, Mylan, Novartis, Orion Biotechnology, Polpharma, Population Council, Receptos/Celgene, Roche/Genentech, Sanofi/Genzyme, Teva, and TG Therapeutics.
JAC: received personal compensation for consulting from Biogen, Bristol Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and Pharmaceutical Security Institute; speaking from H3 Communication; and serving as an editor of Multiple Sclerosis Journal.
DTR: received grant support from Takeda; served as a consultant for AbbVie, AltruBio, Arena Pharmaceuticals, Bristol Myers Squibb, Eli Lilly, Genentech/Roche, Gilead Sciences, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Takeda, and TechLab.
This study was sponsored and funded by Bristol Myers Squibb.