2023 American Academy of Neurology Abstract Website

Bruce A. C. Cree¹, Silvio Danese², Douglas C. Wolf³, Olga Alekseeva⁴, Lorna Charles⁵, AnnKatrin Petersen⁵, James K. Sheffield⁵, Chun-Yen Cheng⁵, Jon V. Riolo⁵, Diego Silva⁵, Fred D. Lublin⁶, David T. Rubin⁷, Jeffrey A. Cohen⁸
¹Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, ²Humanitas University, Milan, Italy, ³Atlanta Gastroenterology Associates, LLC, Atlanta, Georgia, ⁴Nizhegorodskaya Regional Clinical, Nizhegorodskaya oblast' Russia, ⁵Bristol Myers Squibb, Princeton, New Jersey, ⁶Mount Sinai Medical Center, New York, New York, ⁷University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois, ⁸Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio

Objective:

Evaluate tolerability/safety of extended ozanimod 0.92 mg/day treatment in adults with relapsing multiple sclerosis (RMS) or moderately to severely active ulcerative colitis (UC).

Background:

Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved for treatment of RMS or moderately to severely active UC.

Design/Methods:

The RMS population included patients treated with ozanimod 0.92 mg in DAYBREAK (NCT02576717; 10/16/2015 through 2/1/2022), an ongoing open-label extension (OLE) trial of patients from phase 1‒3 ozanimod studies. The UC population included pooled patients treated with ozanimod 0.92 mg in phase 2 (NCT01647516), phase 3 (NCT02435992), and respective OLE trials through May 5, 2022. Safety outcomes included treatment-emergent adverse events (TEAEs) and TEAEs of special interest based on association with S1P modulation.

Results:

Mean (SD) ozanimod exposure during DAYBREAK among 2494 patients with RMS was 56.4 (15.9) months (11,732.2 patient-years [PY]); exposure in 1158 UC patients was 28.4 (23.3) months (2714.9 PY) (MS/UC combined: 14,447.1 PY). TEAEs occurred in 88.2% of RMS and 74.6% of UC patients. Serious TEAEs were reported in 14.1% and 17.3%, and TEAEs leading to ozanimod discontinuation in 3.6% and 9.3%, respectively. The most common TEAS were nasopharyngitis (20.6%; exposure-adjusted incidence rate [IR] 51.0/1000 PY), headache (16.9%; 40.3/1000 PY), and upper respiratory infection (11.9%; 27.3/1000 PY) in RMS patients, and lymphopenia (12.3%; 53.6/1000 PY), anemia (8.4%; 35.0/1000 PY), lymphocyte count decreased (7.9%; 33.2/1000 PY), and nasopharyngitis (7.9%; 33.2/1000 PY) in UC patients. In MS and UC, respectively, IRs/1000 PY were 229.3 and 194.6 for any infection, 8.4 and 15.2 for serious infection, 13.5 and 11.8 for opportunistic infection, and 3.3 and 6.2 for malignancy. Alanine aminotransferase levels >5× upper limit of normal occurred in 0.8% and 2.3% of RMS and UC patients.

Conclusions:

Long-term ozanimod 0.92 mg/day was generally well tolerated and safe for most patients with RMS or moderately to severely active UC.