Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: results from the DAYBREAK open-label extension study
ECTRIMS Online Library. Steinman L. 09/12/19; 278233; P1031
Lawrence Steinman
Lawrence Steinman
Contributions
Abstract

Abstract: P1031

Type: Poster Sessions

Abstract Category: Therapy - Long-term treatment monitoring

L. Steinman1, G. Comi2, A. Bar-Or3, K.W. Selmaj4, D.L. Arnold5, H.-P. Hartung6, X. Montalban7, E.K. Havrdová8, J.K. Sheffield9, N. Minton9, A. Janjua9, V. Huang9, D. Silva9, L. Kappos10, J.A. Cohen11, B.A.C. Cree12

1Departments of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, CA, United States, 2Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 3Center for Neuroinflammation and Experimental Therapeutics, and Multiple Sclerosis Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 4Center for Neurology, Łódź, Poland and Collegium Medicum, Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland, 5NeuroRx Research and Montréal Neurological Institute, McGill University, Montréal, QC, Canada, 6Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany, 7Division of Neurology, St Michael's Hospital, University of Toronto, Toronto, Canada, and Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitario Vall d'Hebron, Barcelona, Spain, 8Department of Neurology and Center for Clinical Neuroscience, First Medical Faculty, Charles University, Prague, Czech Republic, 9Celgene Corporation, Summit, NJ, United States, 10Neurologic Clinic and Policlinic, University Hospital and University of Basel, Basel, Switzerland, 11Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, OH, 12Weill Institute for Neurosciences, Department of Neurology, UCSF University of California San Francisco, San Francisco, CA, United States

Introduction: Ozanimod, an oral, once-daily selective agonist for the sphingosine 1-phosphate receptors 1 and 5, has been evaluated for treatment of relapsing multiple sclerosis (RMS) in clinical pharmacology and in phase 2 and 3 efficacy and safety studies.
Objectives: An ongoing open-label extension (OLE) study was designed to characterise the long-term safety and efficacy of ozanimod in participants with previous experience in the clinical development program of ozanimod for RMS.
Methods: Participants with RMS who completed 1 of 4 parent trials were eligible to enroll in the OLE, where they received ozanimod HCl 1 mg. Though the primary objective of the OLE was evaluation of safety, for the efficacy evaluation, the primary endpoint was the annualised relapse rate (ARR) calculated via negative binomial regression. Efficacy data were summarised by pooled parent-trial treatment group (n, ITT population): placebo followed by ozanimod HCl 0.5 mg/d (n=37) or 1 mg/d (n=35), intramuscular interferon β-1a (IFN) 30 µg/wk (n=740), or ozanimod HCl 0.5 mg/d (n=838) or 1 mg/d (n=844). Safety assessments included treatment-emergent adverse event (TEAE) monitoring.
Results: In total, 2,639 participants completed the parent trials; this interim analysis (data cutoff 30/6/18) of the OLE included 2,494 participants with mean (range) ozanimod exposure of 19.0 (0.03-32.5) mo in the OLE. In phase 3 parent trials (12─24 mo), mean ARR was 0.153 (95% CI, 0.125‒0.187) with ozanimod HCl 1 mg and 0.246 (0.204‒0.297) with IFN. Among participants who received ozanimod HCl 1 mg in any parent trial, ARR with continued ozanimod HCl 1 mg in the OLE (additional 19.2 mo of exposure) was 0.126 (0.099─0.161). Among those who received IFN in parent trials, mean ARR was reduced to 0.123 (0.095‒0.158) after switching to ozanimod in the OLE (mean exposure 18.3 mo). In the OLE, 1,704 participants (68.3%) had any TEAE, 144 (5.8%) had a serious TEAE, and 30 (1.2%) discontinued due to a TEAE. Similar rates of TEAEs and serious TEAEs occurred when assessed by parent-trial treatment groups, and findings were generally consistent with the phase 3 studies. The most common TEAE was nasopharyngitis (11.7%).
Conclusions: Continuing or switching to ozanimod HCl 1 mg was associated with a low ARR in this OLE study. Ozanimod was generally well tolerated; no new safety concerns were raised. These data support ozanimod as a potential safe and effective oral therapy option for patients with RMS.
Disclosure: LS reports consulting for AbbVie, Atreca, Celgene Corporation, Novartis, Teva, Tolerion, and EMD Serono, and research support from Atara, Biogen, and Celgene Corporation. GC reports compensation for consulting and/or speaking activities from Almirall, Biogen, Celgene Corporation, EXCEMED, Forward Pharm, Genzyme, Merck, Novartis, Roche, Sanofi, and Teva. ABO reports personal compensation for consulting for Biogen, Celgene Corporation, EMD Serono, Genzyme, MedImmune, Novartis, and Roche. KWS reports consulting for Biogen, Celgene Corporation, Genzyme, Merck, Novartis, Ono Pharma, Roche, Synthon, and Teva. DLA reports personal fees for consulting from Acorda, Biogen, Celgene Corporation, MedImmune, Mitsubishi Pharma, Novartis, Roche, and Sanofi; grant support from Biogen and Novartis; and equity interest in NeuroRx Research. HPH reports personal fees for consulting, serving on steering committees, and speaking from Bayer Healthcare, Biogen, Celgene Corporation, GeNeuro, Genzyme, Merck, MedImmune, Novartis, Octapharma, Opexa, Roche, Sanofi, and Teva. XM has received speaking honoraria and travel expenses for scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past 3 years with Biogen Idec, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, Roche, Celgene, Actelion, NMSS and MSIF. EKH reports personal compensation for consulting and speaking for Actelion, Biogen, Celgene Corporation, Merck, Novartis, Roche, Sanofi, and Teva, and is supported by Czech Ministry of Education, project PROGRES Q27/LF1. JKS is an employee of Celgene Corporation. NM is an employee of Celgene Corporation. AJ is an employee of Celgene Corporation. VH is an employee of Celgene Corporation. DS is an employee of Celgene Corporation. LK's institution (University Hospital Basel) has received the following, which was used exclusively for research support: steering committee, advisory board, and consultancy fees (Actelion, Addex, Bayer, Biogen, Biotica, Celgene Corporation, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport); speaker fees (Bayer, Biogen, Merck, Novartis, Sanofi, and Teva); support of educational activities (Bayer, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva); license fees for Neurostatus products; and grants (Bayer, Biogen, European Union, Innoswiss, Merck, Novartis, Roche, Swiss MS Society, and Swiss National Research Foundation). JAC reports personal compensation for consulting for Alkermes, Biogen, Convelo, EMD Serono, ERT, Gossamer Bio, Novartis, and ProValuate; speaking for Mylan and Synthon; and serving as an Editor of Multiple Sclerosis Journal. BACC reports personal compensation for consulting for AbbVie, Akili, EMD Serono, GeNeuro, Novartis, Sanofi Genzyme, and TG Therapeutics.
This study was funded by Celgene International II Sàrl.

Abstract: P1031

Type: Poster Sessions

Abstract Category: Therapy - Long-term treatment monitoring

L. Steinman1, G. Comi2, A. Bar-Or3, K.W. Selmaj4, D.L. Arnold5, H.-P. Hartung6, X. Montalban7, E.K. Havrdová8, J.K. Sheffield9, N. Minton9, A. Janjua9, V. Huang9, D. Silva9, L. Kappos10, J.A. Cohen11, B.A.C. Cree12

1Departments of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, CA, United States, 2Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 3Center for Neuroinflammation and Experimental Therapeutics, and Multiple Sclerosis Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 4Center for Neurology, Łódź, Poland and Collegium Medicum, Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland, 5NeuroRx Research and Montréal Neurological Institute, McGill University, Montréal, QC, Canada, 6Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany, 7Division of Neurology, St Michael's Hospital, University of Toronto, Toronto, Canada, and Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitario Vall d'Hebron, Barcelona, Spain, 8Department of Neurology and Center for Clinical Neuroscience, First Medical Faculty, Charles University, Prague, Czech Republic, 9Celgene Corporation, Summit, NJ, United States, 10Neurologic Clinic and Policlinic, University Hospital and University of Basel, Basel, Switzerland, 11Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, OH, 12Weill Institute for Neurosciences, Department of Neurology, UCSF University of California San Francisco, San Francisco, CA, United States

Introduction: Ozanimod, an oral, once-daily selective agonist for the sphingosine 1-phosphate receptors 1 and 5, has been evaluated for treatment of relapsing multiple sclerosis (RMS) in clinical pharmacology and in phase 2 and 3 efficacy and safety studies.
Objectives: An ongoing open-label extension (OLE) study was designed to characterise the long-term safety and efficacy of ozanimod in participants with previous experience in the clinical development program of ozanimod for RMS.
Methods: Participants with RMS who completed 1 of 4 parent trials were eligible to enroll in the OLE, where they received ozanimod HCl 1 mg. Though the primary objective of the OLE was evaluation of safety, for the efficacy evaluation, the primary endpoint was the annualised relapse rate (ARR) calculated via negative binomial regression. Efficacy data were summarised by pooled parent-trial treatment group (n, ITT population): placebo followed by ozanimod HCl 0.5 mg/d (n=37) or 1 mg/d (n=35), intramuscular interferon β-1a (IFN) 30 µg/wk (n=740), or ozanimod HCl 0.5 mg/d (n=838) or 1 mg/d (n=844). Safety assessments included treatment-emergent adverse event (TEAE) monitoring.
Results: In total, 2,639 participants completed the parent trials; this interim analysis (data cutoff 30/6/18) of the OLE included 2,494 participants with mean (range) ozanimod exposure of 19.0 (0.03-32.5) mo in the OLE. In phase 3 parent trials (12─24 mo), mean ARR was 0.153 (95% CI, 0.125‒0.187) with ozanimod HCl 1 mg and 0.246 (0.204‒0.297) with IFN. Among participants who received ozanimod HCl 1 mg in any parent trial, ARR with continued ozanimod HCl 1 mg in the OLE (additional 19.2 mo of exposure) was 0.126 (0.099─0.161). Among those who received IFN in parent trials, mean ARR was reduced to 0.123 (0.095‒0.158) after switching to ozanimod in the OLE (mean exposure 18.3 mo). In the OLE, 1,704 participants (68.3%) had any TEAE, 144 (5.8%) had a serious TEAE, and 30 (1.2%) discontinued due to a TEAE. Similar rates of TEAEs and serious TEAEs occurred when assessed by parent-trial treatment groups, and findings were generally consistent with the phase 3 studies. The most common TEAE was nasopharyngitis (11.7%).
Conclusions: Continuing or switching to ozanimod HCl 1 mg was associated with a low ARR in this OLE study. Ozanimod was generally well tolerated; no new safety concerns were raised. These data support ozanimod as a potential safe and effective oral therapy option for patients with RMS.
Disclosure: LS reports consulting for AbbVie, Atreca, Celgene Corporation, Novartis, Teva, Tolerion, and EMD Serono, and research support from Atara, Biogen, and Celgene Corporation. GC reports compensation for consulting and/or speaking activities from Almirall, Biogen, Celgene Corporation, EXCEMED, Forward Pharm, Genzyme, Merck, Novartis, Roche, Sanofi, and Teva. ABO reports personal compensation for consulting for Biogen, Celgene Corporation, EMD Serono, Genzyme, MedImmune, Novartis, and Roche. KWS reports consulting for Biogen, Celgene Corporation, Genzyme, Merck, Novartis, Ono Pharma, Roche, Synthon, and Teva. DLA reports personal fees for consulting from Acorda, Biogen, Celgene Corporation, MedImmune, Mitsubishi Pharma, Novartis, Roche, and Sanofi; grant support from Biogen and Novartis; and equity interest in NeuroRx Research. HPH reports personal fees for consulting, serving on steering committees, and speaking from Bayer Healthcare, Biogen, Celgene Corporation, GeNeuro, Genzyme, Merck, MedImmune, Novartis, Octapharma, Opexa, Roche, Sanofi, and Teva. XM has received speaking honoraria and travel expenses for scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past 3 years with Biogen Idec, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, Roche, Celgene, Actelion, NMSS and MSIF. EKH reports personal compensation for consulting and speaking for Actelion, Biogen, Celgene Corporation, Merck, Novartis, Roche, Sanofi, and Teva, and is supported by Czech Ministry of Education, project PROGRES Q27/LF1. JKS is an employee of Celgene Corporation. NM is an employee of Celgene Corporation. AJ is an employee of Celgene Corporation. VH is an employee of Celgene Corporation. DS is an employee of Celgene Corporation. LK's institution (University Hospital Basel) has received the following, which was used exclusively for research support: steering committee, advisory board, and consultancy fees (Actelion, Addex, Bayer, Biogen, Biotica, Celgene Corporation, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport); speaker fees (Bayer, Biogen, Merck, Novartis, Sanofi, and Teva); support of educational activities (Bayer, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva); license fees for Neurostatus products; and grants (Bayer, Biogen, European Union, Innoswiss, Merck, Novartis, Roche, Swiss MS Society, and Swiss National Research Foundation). JAC reports personal compensation for consulting for Alkermes, Biogen, Convelo, EMD Serono, ERT, Gossamer Bio, Novartis, and ProValuate; speaking for Mylan and Synthon; and serving as an Editor of Multiple Sclerosis Journal. BACC reports personal compensation for consulting for AbbVie, Akili, EMD Serono, GeNeuro, Novartis, Sanofi Genzyme, and TG Therapeutics.
This study was funded by Celgene International II Sàrl.

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