Abstract: P869
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Ozanimod, an oral, once-daily immunomodulator that selectively targets sphingosine 1-phosphate receptors 1 and 5 (S1P1,5), significantly reduced adjusted annualised relapse rate (ARR) vs interferon β-1a (IFN) in two phase 3 studies in patients with relapsing multiple sclerosis (RMS). Severe relapses are associated with accrual of disability (Wang 2016). Steroid treatment and hospitalisation are potential proxies for severe relapse (Freedman 2016). Decreasing relapses may reduce physical disability accumulation (Lublin 2014). We report results of a post-hoc pooled analysis of relapses, including severe relapses, from the phase 3 SUNBEAM and RADIANCE trials.
Methods: Ozanimod HCl 1 and 0.5 mg (equivalent to ozanimod 0.92 and 0.46 mg, respectively) vs IFN 30 µg was evaluated for ≥12 (SUNBEAM) or 24 months (RADIANCE). Relapse was defined as new or worsening neurological symptoms persisting >24 hours accompanied by Expanded Disability Status Scale increase of ≥0.5 overall, ≥2 on one Function System (FS) score, or ≥1 on two FS scores. Severe relapses were defined here as requiring steroid treatment or hospitalisation. ARR was compared using a Poisson regression model, adjusted for study, region, baseline age, and baseline gadolinium-enhancing lesions. Percent of patients with relapse was compared using log-rank test.
Results: 2659 patients were randomised and treated (ozanimod HCl 1 mg, n=880; 0.5 mg, n=890, IFN, n=889). Ozanimod HCl 1 mg and 0.5 mg reduced adjusted overall ARR by 42% (0.18; P< 0.0001) and 26% (0.23; P< 0.0001), respectively, vs IFN (0.30). The vast majority (96%) of confirmed relapses reported required steroid treatment or hospitalization. In the post-hoc analysis, adjusted ARR requiring steroids or hospitalisation was reduced by 43% (ozanimod HCl 1 mg: 0.15; P< 0.0001) and 26% (ozanimod HCl 0.5 mg: 0.20; P< 0.0001) vs IFN (0.27). The percents of patients with relapses requiring steroid or hospitalisation were lower with ozanimod HCl 1 mg (20.1%, P< 0.0001) and 0.5 mg (23.3%, P=0.008) vs IFN (30.7%).
Conclusions: In this pooled analysis of two phase 3 studies, ozanimod significantly reduced the rate of relapses, including the present definition of severe relapses, vs IFN in patients with RMS. These data support the potential of ozanimod as an effective oral treatment to reduce the rate of relapse, including severe relapse, in patients with RMS.
Disclosure: Dr. Giancarlo Comi has received compensation for consulting and/or speaking activities from Almirall, Biogen, Celgene Corporation, EXCEMED, Forward Pharm, Genzyme, Merck, Novartis, Roche, Sanofi, and Teva. Dr. Ludwig Kappos´s institution (University Hospital Basel) has received the following in the last 3 years, which was used exclusively for research support: steering committee, advisory board, and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene Corporation, df-mp, EXCEMED, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, and Vianex and royalties for Neurostatus-UHB products. The research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union, and the Roche Research Foundation. Dr. Hans-Peter Hartung has received personal fees for consulting, serving on steering committees and speaking from Bayer, Biogen, GeNeuro, Genzyme, Merck, MedImmune, Novartis, Octapharma, Opexa, Roche, Sanofi, and Teva. Dr. Bruce A.C. Cree has received personal compensation for consulting for Abbvie, Biogen, EMD Serono, GeNeuro, Novartis, and Sanofi Genzyme. Dr. Krzysztof W. Selmaj has served as a consultant for Biogen, Celgene Corporation, Genzyme, Merck, Novartis, Ono Pharma, Roche, Synthon, and Teva. Dr. Amit Bar-Or has received personal compensation for consulting from Biogen, Celgene Corporation, EMD Serono, Genzyme, MedImmune, Novartis, and Roche. Dr. Lawrence Steinman has served as a consultant for Abbvie, Atreca, Celgene Corporation, Novartis, Teva, Tolerion, and EMD Serono, and has received research support from Atara, Biogen, and Celgene Corporation. Dr. Douglas L. Arnold has received personal fees for consulting from Acorda, Biogen, Celgene Corporation, MedImmune, Mitsubishi Pharma, Novartis, Roche, and Sanofi; grant support from Biogen and Novartis; and holds an equity interest in NeuroRx research. Dr. Xavier Montalbán has received speaking honoraria and travel expenses for scientific meetings or has participated in steering committees or in advisory boards for clinical trials with Almirall, Bayer Schering Pharma, Biogen, Genentech, Genzyme, GSK, Merck Serono, MS International Federation, National Multiple Sclerosis Society, Novartis, Roche, Sanofi-Aventis, and Teva, and is the editor for Clinical Cases for Multiple Sclerosis Journal. Dr. Eva K. Havrdová has received personal compensation for consulting and speaking for Actelion, Biogen, Celgene Corporation, Merck, Novartis, Roche, Sanofi, and Teva, and is supported by the Czech Ministry of Education, project PROGRES Q27/LF1. Dr. James K. Sheffield is a salaried employee of Celgene Corporation. Dr. Denise Campagnolo is a salaried employee of Celgene Corporation. Ms. Beatrice Ferguson is a salaried employee of Celgene Corporation. Dr. Jeffrey A. Cohen has received personal compensation for consulting for Adamas, Celgene Corporation, Novartis, and PendoPharma, and as a Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical.
Abstract: P869
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Ozanimod, an oral, once-daily immunomodulator that selectively targets sphingosine 1-phosphate receptors 1 and 5 (S1P1,5), significantly reduced adjusted annualised relapse rate (ARR) vs interferon β-1a (IFN) in two phase 3 studies in patients with relapsing multiple sclerosis (RMS). Severe relapses are associated with accrual of disability (Wang 2016). Steroid treatment and hospitalisation are potential proxies for severe relapse (Freedman 2016). Decreasing relapses may reduce physical disability accumulation (Lublin 2014). We report results of a post-hoc pooled analysis of relapses, including severe relapses, from the phase 3 SUNBEAM and RADIANCE trials.
Methods: Ozanimod HCl 1 and 0.5 mg (equivalent to ozanimod 0.92 and 0.46 mg, respectively) vs IFN 30 µg was evaluated for ≥12 (SUNBEAM) or 24 months (RADIANCE). Relapse was defined as new or worsening neurological symptoms persisting >24 hours accompanied by Expanded Disability Status Scale increase of ≥0.5 overall, ≥2 on one Function System (FS) score, or ≥1 on two FS scores. Severe relapses were defined here as requiring steroid treatment or hospitalisation. ARR was compared using a Poisson regression model, adjusted for study, region, baseline age, and baseline gadolinium-enhancing lesions. Percent of patients with relapse was compared using log-rank test.
Results: 2659 patients were randomised and treated (ozanimod HCl 1 mg, n=880; 0.5 mg, n=890, IFN, n=889). Ozanimod HCl 1 mg and 0.5 mg reduced adjusted overall ARR by 42% (0.18; P< 0.0001) and 26% (0.23; P< 0.0001), respectively, vs IFN (0.30). The vast majority (96%) of confirmed relapses reported required steroid treatment or hospitalization. In the post-hoc analysis, adjusted ARR requiring steroids or hospitalisation was reduced by 43% (ozanimod HCl 1 mg: 0.15; P< 0.0001) and 26% (ozanimod HCl 0.5 mg: 0.20; P< 0.0001) vs IFN (0.27). The percents of patients with relapses requiring steroid or hospitalisation were lower with ozanimod HCl 1 mg (20.1%, P< 0.0001) and 0.5 mg (23.3%, P=0.008) vs IFN (30.7%).
Conclusions: In this pooled analysis of two phase 3 studies, ozanimod significantly reduced the rate of relapses, including the present definition of severe relapses, vs IFN in patients with RMS. These data support the potential of ozanimod as an effective oral treatment to reduce the rate of relapse, including severe relapse, in patients with RMS.
Disclosure: Dr. Giancarlo Comi has received compensation for consulting and/or speaking activities from Almirall, Biogen, Celgene Corporation, EXCEMED, Forward Pharm, Genzyme, Merck, Novartis, Roche, Sanofi, and Teva. Dr. Ludwig Kappos´s institution (University Hospital Basel) has received the following in the last 3 years, which was used exclusively for research support: steering committee, advisory board, and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene Corporation, df-mp, EXCEMED, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, and Vianex and royalties for Neurostatus-UHB products. The research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union, and the Roche Research Foundation. Dr. Hans-Peter Hartung has received personal fees for consulting, serving on steering committees and speaking from Bayer, Biogen, GeNeuro, Genzyme, Merck, MedImmune, Novartis, Octapharma, Opexa, Roche, Sanofi, and Teva. Dr. Bruce A.C. Cree has received personal compensation for consulting for Abbvie, Biogen, EMD Serono, GeNeuro, Novartis, and Sanofi Genzyme. Dr. Krzysztof W. Selmaj has served as a consultant for Biogen, Celgene Corporation, Genzyme, Merck, Novartis, Ono Pharma, Roche, Synthon, and Teva. Dr. Amit Bar-Or has received personal compensation for consulting from Biogen, Celgene Corporation, EMD Serono, Genzyme, MedImmune, Novartis, and Roche. Dr. Lawrence Steinman has served as a consultant for Abbvie, Atreca, Celgene Corporation, Novartis, Teva, Tolerion, and EMD Serono, and has received research support from Atara, Biogen, and Celgene Corporation. Dr. Douglas L. Arnold has received personal fees for consulting from Acorda, Biogen, Celgene Corporation, MedImmune, Mitsubishi Pharma, Novartis, Roche, and Sanofi; grant support from Biogen and Novartis; and holds an equity interest in NeuroRx research. Dr. Xavier Montalbán has received speaking honoraria and travel expenses for scientific meetings or has participated in steering committees or in advisory boards for clinical trials with Almirall, Bayer Schering Pharma, Biogen, Genentech, Genzyme, GSK, Merck Serono, MS International Federation, National Multiple Sclerosis Society, Novartis, Roche, Sanofi-Aventis, and Teva, and is the editor for Clinical Cases for Multiple Sclerosis Journal. Dr. Eva K. Havrdová has received personal compensation for consulting and speaking for Actelion, Biogen, Celgene Corporation, Merck, Novartis, Roche, Sanofi, and Teva, and is supported by the Czech Ministry of Education, project PROGRES Q27/LF1. Dr. James K. Sheffield is a salaried employee of Celgene Corporation. Dr. Denise Campagnolo is a salaried employee of Celgene Corporation. Ms. Beatrice Ferguson is a salaried employee of Celgene Corporation. Dr. Jeffrey A. Cohen has received personal compensation for consulting for Adamas, Celgene Corporation, Novartis, and PendoPharma, and as a Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical.