Ozanimod vs interferon β-1a: clinical and MRI results of RADIANCE part B - A 2-year Phase 3 trial in relapsing multiple sclerosis
ECTRIMS Online Library. Cohen J. Oct 28, 2017; 202644; 280
Jeffrey Cohen
Jeffrey Cohen
Contributions
Abstract

Abstract: 280

Type: Oral

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). We report the results from RADIANCE Part B, the second of two Phase 3 studies conducted in RMS patients to evaluate the efficacy and safety of ozanimod compared to interferon (IFN) β-1a.
Methods: A 24 month, multicenter, randomized, double-blind, parallel-group, active treatment-controlled study was conducted of daily oral ozanimod 1 or 0.5 mg vs. weekly IFN β-1a, 30 µg IM injection. Treatment was initiated with a 7-day dose escalation. The primary endpoint was annualized relapse rate (ARR) at month 24 for each ozanimod dose vs. IFN β‑1a. Key secondary endpoints included MRI assessments to measure T2 lesion changes and gadolinium enhancing (GdE) T1 lesions. Disability will be evaluated on a pooled dataset with a second Phase 3 trial.
Results: A total of 1,313 patients were randomized and treated, with baseline characteristics similar across treatment groups and similar to recent Phase 3 trials in RMS: mean age 36 years, 67% female, mean EDSS 2.5, mean number of relapses in prior year of 1.3, 43% with GdE lesions, and 29% previously treated with disease-modifying therapy. 90% of ozanimod 1 mg patients and 85% of 0.5 mg patients vs. 85% of IFN β-1a patients completed the trial. Both doses (1 and 0.5 mg) reduced ARR (0.172 and 0.218) compared with IFN β-1a (0.276) (p< 0.0001, p=0.0168, respectively). The adjusted mean number of new or enlarging T2 lesions per scan was reduced for ozanimod 1 mg (1.848) and 0.5 mg (2.082) compared with IFN β-1a (3.183) by 42% and 35%, respectively (p< 0.0001 for both comparisons). The adjusted mean number of GdE lesions at 24 months was also reduced for ozanimod 1 mg (0.175) and 0.5 mg (0.196) compared with IFN β-1a (0.373) by 53% (p=0.0006) and 47% (p=0.0029), respectively. The incidence of adverse events (AEs), serious AEs, and AEs leading to discontinuation was balanced across treatment groups. Similar cardiac and infection profiles were observed across treatment groups.
Conclusion: In this Phase 3 study, both doses of ozanimod demonstrated superiority to interferon β-1a on relapse and MRI endpoints over 2 years in an active RMS population. These findings, coupled with the safety and tolerability results, demonstrate that ozanimod has the potential to provide a safe and effective oral therapy option for RMS patients.
Disclosure: Clinical Trials.gov: NCT02294058 (completed)
J.A .Cohen: Consultancy: Genentech, Genzyme, Merck, Novartis, Receptos, and Multiple Sclerosis Journal - Experimental, Translational and Clinical.
G. Comi: Consultancy: Almirall, Biogen, Celgene Corporation, EXCEMED, Forward Pharm, Genzyme, Merck, Novartis, Receptos, Roche, Sanofi, and Teva.
K. 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 HealthCare, Biogen, CSL Behring, GeNeuro, Medimmune, Merck, Novartis, Ocatapharma, Opexa Therapeutics, Receptos/Celgene, Roche, Sanofi Genzyme, Teva.
X. Montalban: 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. K. Havrdova: 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 PROGRES Q27/LF1.
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. K. Sheffield: Shareholder: Celgene.
K Raghupathi: Shareholder: Celgene.
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 Foundation.

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