Abstract: 232
Type: Oral
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Ozanimod (RPC1063), is an oral, once daily immunomodulator that selectively targets sphingosine 1-phosphate 1 and 5 receptors in clinical development for treatment of relapsing multiple sclerosis (RMS). Two Phase 3 studies were initiated to evaluate the efficacy and safety of ozanimod compared to interferon β-1a. In the SUNBEAM study, drug was administered for at least 1 year in patients with RMS.
Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-group, active treatment-controlled, study of daily oral ozanimod 0.5 or 1 mg vs. weekly IFN β-1a, 30 µg IM injection. Treatment with ozanimod was initiated with a 7-day dose escalation. The primary endpoint was annualized relapse rate (ARR) for each ozanimod dose vs IFN β-1a. Key secondary endpoints included magnetic resonance imaging (MRI) assessments to measure new and enlarging T2 lesions from baseline to month 12 and T1, gadolinium enhancing lesions (GdE) at month 12. Disability progression, based on Expanded Disability Status Scale (EDSS), was pre-specified to be evaluated using a pooled analysis of both Phase 3 studies.
Results: A total of 1,346 RMS patients were enrolled in 20 countries with baseline characteristics similar across treatment groups. At baseline prior to randomization: mean age of 36 years, 66% female, mean EDSS score of 2.6, mean number of relapses of 1.3 in the prior year, 47% with GdE lesions and 31% were previously treated with disease-modifying therapy. Mean treatment duration was 13.6 months. Both ozanimod 0.5 and 1 mg treatment groups demonstrated statistically significant reductions compared to IFN β-1a in ARR. The number of new or enlarging T2 lesions and the adjusted mean number of GdE at month 12 demonstrated a significant reduction for both ozanimod groups compared to IFN β-1a. A consistent dose response was observed across efficacy endpoints for the two ozanimod doses. Most treatment-emergent adverse events (AEs) were mild, with a low incidence of serious AEs, and similar across treatment groups. The rate of discontinuation due to AEs was also low and similar across treatment groups. No first dose, clinically relevant cases of bradycardia and no AVB of 2nd degree or higher were reported.
Conclusion: In this Phase 3 study, both doses of ozanimod demonstrated superiority to IFN β-1a on relapse and MRI endpoints. This, coupled with the safety and tolerability results, demonstrates a favourable benefit risk profile for ozanimod in RMS.
Disclosure: G. Comi, Consultancy: Almirall, Biogen, Celgene Corporation, EXCEMED, Forward Pharm, Genzyme, Merck, Novartis, Receptos, Roche, Sanofi, and Teva.
L. Kappos, Research support: steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; royalties from Neurostatus Systems GmbH and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundatio.
K.W. Selmaj, Consultancy: Biogen Idec, Genzyme, Merck, Novartis, Ono Pharma, Roche, Synthon, Teva, and Receptos.
A. Bar-Or, Consultancy: Amplimmune, Aventis, Bayhill Therapeutics, Berlex/Bayer, Biogen Idec, BioMS, DioGenix, Eli Lilly, EMD Serono, Genentech, Genzyme, GlaxoSmithKline, Guthy-Jackson/GGF, MedImmune, Mitsubishi Pharma, Novartis, Ono Pharma, Receptos, Roche, Sanofi-Aventis, Teva, and Wyeth. Dr. Bar-Or has received grant support from Amplimmune, Biogen Idec, Diogenix, Genentech, Sanofi- Genzyme, GlaxoSmithKline, Novartis, Ono Pharma, Teva Neuroscience, Receptos Inc., Roche, and Merck/EMD Serono .
D.L. Arnold, Consultancy: Acorda, Biogen, Hoffmann-LaRoche, MedImmune, Mitsubishi Pharma, Novartis, Receptos, and Sanofi-Aventis; grants from Biogen and Novartis; and an equity interest in NeuroRx Research.
L. Steinman, Consultancy: Novartis, Receptos/Celgene, Atreca, Tolerion, Teva, Abbvie, EMD Serono and received research support from Atara, Celgene and Biogen .
H-P Hartung, Consulting and/or speaking fees from Bayer, Biogen, CSL Behring, Grifols, Merck Serono, Novartis, Roche, and Sanofi Genzyme.
X. Montalbán, Personal compensation for activities with Actelion, Almirall, Bayer Pharmaceuticals, Biogen Idec, Genzyme Corporation, Merck & Co., Inc., NeuroTex, Novartis, Octopharma, Receptos, and Roche Diagnostics Corporation as a speaker.
E. Havrdová, Personal compensation for activities with Actelion, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva as a speaker. Dr. Havrdova has received research support from Czech Ministry of Education of Czech Republic, project PRVOUK-P26/LF1/1.
B. A. C. Cree, Consultancy: Abbvie, Biogen Idec, EMD Serono, MedImmune, Novartis, Genzyme/Sanofi aventis, Teva and received research support from Acorda, Biogen Idec, EMD Serono, Hoffman La Roche, MedImmune, Novartis and Teva.
J. Sheffield, Shareholder: Celgene.
K. Raghupathi, Shareholder, Celgene.
J. A. Cohen, Consultancy: Genentech, Genzyme, Merck, Novartis, Receptos, and Multiple Sclerosis Journal - Experimental, Translational and Clinical.
Abstract: 232
Type: Oral
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Ozanimod (RPC1063), is an oral, once daily immunomodulator that selectively targets sphingosine 1-phosphate 1 and 5 receptors in clinical development for treatment of relapsing multiple sclerosis (RMS). Two Phase 3 studies were initiated to evaluate the efficacy and safety of ozanimod compared to interferon β-1a. In the SUNBEAM study, drug was administered for at least 1 year in patients with RMS.
Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-group, active treatment-controlled, study of daily oral ozanimod 0.5 or 1 mg vs. weekly IFN β-1a, 30 µg IM injection. Treatment with ozanimod was initiated with a 7-day dose escalation. The primary endpoint was annualized relapse rate (ARR) for each ozanimod dose vs IFN β-1a. Key secondary endpoints included magnetic resonance imaging (MRI) assessments to measure new and enlarging T2 lesions from baseline to month 12 and T1, gadolinium enhancing lesions (GdE) at month 12. Disability progression, based on Expanded Disability Status Scale (EDSS), was pre-specified to be evaluated using a pooled analysis of both Phase 3 studies.
Results: A total of 1,346 RMS patients were enrolled in 20 countries with baseline characteristics similar across treatment groups. At baseline prior to randomization: mean age of 36 years, 66% female, mean EDSS score of 2.6, mean number of relapses of 1.3 in the prior year, 47% with GdE lesions and 31% were previously treated with disease-modifying therapy. Mean treatment duration was 13.6 months. Both ozanimod 0.5 and 1 mg treatment groups demonstrated statistically significant reductions compared to IFN β-1a in ARR. The number of new or enlarging T2 lesions and the adjusted mean number of GdE at month 12 demonstrated a significant reduction for both ozanimod groups compared to IFN β-1a. A consistent dose response was observed across efficacy endpoints for the two ozanimod doses. Most treatment-emergent adverse events (AEs) were mild, with a low incidence of serious AEs, and similar across treatment groups. The rate of discontinuation due to AEs was also low and similar across treatment groups. No first dose, clinically relevant cases of bradycardia and no AVB of 2nd degree or higher were reported.
Conclusion: In this Phase 3 study, both doses of ozanimod demonstrated superiority to IFN β-1a on relapse and MRI endpoints. This, coupled with the safety and tolerability results, demonstrates a favourable benefit risk profile for ozanimod in RMS.
Disclosure: G. Comi, Consultancy: Almirall, Biogen, Celgene Corporation, EXCEMED, Forward Pharm, Genzyme, Merck, Novartis, Receptos, Roche, Sanofi, and Teva.
L. Kappos, Research support: steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; royalties from Neurostatus Systems GmbH and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundatio.
K.W. Selmaj, Consultancy: Biogen Idec, Genzyme, Merck, Novartis, Ono Pharma, Roche, Synthon, Teva, and Receptos.
A. Bar-Or, Consultancy: Amplimmune, Aventis, Bayhill Therapeutics, Berlex/Bayer, Biogen Idec, BioMS, DioGenix, Eli Lilly, EMD Serono, Genentech, Genzyme, GlaxoSmithKline, Guthy-Jackson/GGF, MedImmune, Mitsubishi Pharma, Novartis, Ono Pharma, Receptos, Roche, Sanofi-Aventis, Teva, and Wyeth. Dr. Bar-Or has received grant support from Amplimmune, Biogen Idec, Diogenix, Genentech, Sanofi- Genzyme, GlaxoSmithKline, Novartis, Ono Pharma, Teva Neuroscience, Receptos Inc., Roche, and Merck/EMD Serono .
D.L. Arnold, Consultancy: Acorda, Biogen, Hoffmann-LaRoche, MedImmune, Mitsubishi Pharma, Novartis, Receptos, and Sanofi-Aventis; grants from Biogen and Novartis; and an equity interest in NeuroRx Research.
L. Steinman, Consultancy: Novartis, Receptos/Celgene, Atreca, Tolerion, Teva, Abbvie, EMD Serono and received research support from Atara, Celgene and Biogen .
H-P Hartung, Consulting and/or speaking fees from Bayer, Biogen, CSL Behring, Grifols, Merck Serono, Novartis, Roche, and Sanofi Genzyme.
X. Montalbán, Personal compensation for activities with Actelion, Almirall, Bayer Pharmaceuticals, Biogen Idec, Genzyme Corporation, Merck & Co., Inc., NeuroTex, Novartis, Octopharma, Receptos, and Roche Diagnostics Corporation as a speaker.
E. Havrdová, Personal compensation for activities with Actelion, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva as a speaker. Dr. Havrdova has received research support from Czech Ministry of Education of Czech Republic, project PRVOUK-P26/LF1/1.
B. A. C. Cree, Consultancy: Abbvie, Biogen Idec, EMD Serono, MedImmune, Novartis, Genzyme/Sanofi aventis, Teva and received research support from Acorda, Biogen Idec, EMD Serono, Hoffman La Roche, MedImmune, Novartis and Teva.
J. Sheffield, Shareholder: Celgene.
K. Raghupathi, Shareholder, Celgene.
J. A. Cohen, Consultancy: Genentech, Genzyme, Merck, Novartis, Receptos, and Multiple Sclerosis Journal - Experimental, Translational and Clinical.