Krzysztof W. Selmaj,1 Lawrence Steinman,2 Giancarlo Comi,3 Amit Bar-Or,4 Douglas L. Arnold,5 Hans-Peter Hartung,6 Xavier Montalbán,7 Eva K. Havrdová,8 Anthony Krakovich,9 James K. Sheffield,9 Chun-Yen Cheng,9 Andrew Thorpe,9 Jon V. Riolo,9 Erik DeBoer,9 Ludwig Kappos,10 Jeffrey A. Cohen,11 Bruce A. C. Cree12
1 Center for Neurology, Łódź, Poland, and Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland
2 Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, CA
3 Vita-Salute San Raffaele University and Casa di Cura Igea, Milan, Italy
4 Center for Neuroinflammation and Experimental Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
5 NeuroRx Research and Montréal Neurological Institute, McGill University, Montreal, Quebec, Canada
6 Heinrich-Heine University, Düsseldorf, Germany; Brain and Mind Centre, University of Sydney, Sydney, Australia; Medical University of Vienna, Vienna, Austria, and Palacký University Olomouc, Olomouc, Czech Republic
7 Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d’Hebron, Barcelona, Spain
8 Center for Clinical Neuroscience, Charles University, Prague, Czech Republic
9 Bristol Myers Squibb, Princeton, NJ
10 Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Head, Spine and Neuromedicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital, and University of Basel, Basel, Switzerland
11 Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, OH
12 Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA
Background: Ozanimod (OZA), an oral S1P receptor 1 and 5 modulator, is approved for adults with RMS or moderately to severely active UC.
Objectives: Report safety & efficacy of extended OZA exposure.
Methods: RMS pts completing OZA phase 1-3 trials were eligible for the DAYBREAK open-label extension (OZA 0.92mg/d). Primary objective: safety; TEAEs monitored. ARR calculated via negative binomial regression pooled across parent trial tx groups. New/enlarging T2 & GdE lesions reported for pts from active-controlled phase 3 trials.
Results: Of 2639 pts completing parent trials; 2494 were analyzed in DAYBREAK (mean OZA exposure: 60.9 mos [range; 0.03–81.5];12,664.7 pt-yrs). Any TEAE (2219 [89.0%], serious TEAE (SAE;381 [15.3%]), discontinued due to TEAE (98 [3.9%]). TEAE/SAE rates were similar (by parent trial tx). Most common TEAEs: nasopharyngitis (21.3%), headache (17.1%), COVID-19 (16.5%), URTI (12.4%), consistent with parent trials (excluding COVID-19). Adjusted ARR: 0.098 (95% CI, 0.082‒0.117); 67% relapse-free at mo 72. Confirmed disability progression: 17.2% at 3 & 15.2% at 6 mos. At mo 60, adjusted mean new/enlarging lesions per scan (T2: 0.789–0.932; GdE:0.062–0.077) were similar regardless of parent trial tx.
Conclusions: OZA safety profile was consistent with prior reports. OZA tx demonstrated sustained efficacy for disease activity & progression.
