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Ozanimod for Treating Relapsing–Remitting Multiple Sclerosis [ID1294] ERG Report Copyright 2021 Queen's Printer and Controller of HMSO

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Ozanimod for Treating Relapsing–Remitting Multiple Sclerosis [ID1294] ERG Report Copyright 2021 Queen's Printer and Controller of HMSO Confidential until published Fprofile REPORT REPORT ERG STA ERG STA Ozanimod for treating relapsing– remitting multiple sclerosis Confidential until published This report was commissioned by the NIHR HTA Programme as project number NIHR 17/156/08 Completed 21 January 2020 Updated 2 September 2020 CONFIDENTIAL DATA HAS BEEN REDACTED Copyright belongs to the Liverpool Reviews and Implementation Group Ozanimod for treating relapsing–remitting multiple sclerosis [ID1294] ERG Report Copyright 2021 Queen's Printer and Controller of HMSO. All rights reserved. Page 1 of 98 Confidential until published Title: Ozanimod for treating relapsing–remitting multiple sclerosis [ID1294] Produced by: Liverpool Reviews & Implementation Group (LRiG) Authors: Nigel Fleeman, Senior Research Fellow (Clinical Effectiveness), LRiG, University of Liverpool James Mahon, Director, Coldingham Analytical Services, Berwickshire Sarah Nevitt, Research Associate (Medical Statistician), LRiG, University of Liverpool Sophie Beale, Research Associate, LRiG, University of Liverpool Angela Boland, Director, LRiG, University of Liverpool Rui Duarte, Deputy Director, LRiG, University of Liverpool Rachel Houten, Health Economic Modeller, LRiG, University of Liverpool Joanne McEntee, Senior Medicines Information Pharmacist, North West Medicines Information Centre, Liverpool Ian Pomeroy, Honorary Lecturer, School of Medicine, University of Liverpool and Consultant Neurologist, The Walton Centre NHS Foundation Trust, Liverpool and Warrington Correspondence to: Nigel Fleeman, Research Fellow, Liverpool Reviews and Implementation Group, University of Liverpool, Whelan Building, The Quadrangle, Brownlow Hill, Liverpool L69 3GB Date completed: 21 January 2020 (Updated 2 September 2020) Source of funding: This report was commissioned by the NIHR Systematic Reviews Programme as project number 17/156/08 Acknowledgements: The authors would like to thank Siân Price, Consultant Neurologist at Sheffield Teaching Hospitals NHS Foundation Trust who provided feedback on a draft version of the report. Ozanimod for treating relapsing–remitting multiple sclerosis [ID1294] ERG Report Copyright 2021 Queen's Printer and Controller of HMSO. All rights reserved. Page 2 of 98 Confidential until published Copyright is retained by Celgene for Figures 1, 2 and 3 and text referenced on page 15 Rider on responsibility for report: The views expressed in this report are those of the authors and not necessarily those of the NIHR Systematic Reviews Programme. Any errors are the responsibility of the authors. Declared competing interests of the authors: Within the last 3 years, Ian Pomeroy has received reimbursement for attending the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) conference from Teva UK and Merck and fees for speaking at the Modern Thinking in MS conference from Teva UK. Siân Price has received fees for speaking from the Multiple Sclerosis (MS) Academy and is a member of the Association of British Neurologists Advisory Group on MS and neuroinflammation. This report should be referenced as follows: Fleeman N, Mahon J, Nevitt S, Beale S, Boland A, Duarte R, Houten R, McEntee J, Pomeroy I. Ozanimod for treating relapsing– remitting multiple sclerosis: A Single Technology Appraisal. LRiG, University of Liverpool, 2020 Contributions of authors: Nigel Fleeman Project lead, critical appraisal of the clinical evidence and supervised the final report James Mahon Critical appraisal of the economic model Sarah Nevitt Critical appraisal of the statistical evidence Sophie Beale Critical appraisal of the clinical and economic evidence, editorial input Angela Boland Critical appraisal of the clinical and economic evidence, editorial input Rui Duarte Critical appraisal of the clinical and economic evidence, editorial input Rachel Houten Critical appraisal of the economic evidence Joanne McEntee Critical appraisal of the company submission Ian Pomeroy Clinical advice and critical appraisal of the clinical sections of the company submission Ozanimod for treating relapsing–remitting multiple sclerosis [ID1294] ERG Report Copyright 2021 Queen's Printer and Controller of HMSO. All rights reserved. Page 3 of 98 Confidential until published Table of contents List of tables .......................................................................................................................... 5 List of figures ........................................................................................................................ 5 List of abbreviations .............................................................................................................. 6 1 SUMMARY .................................................................................................................... 7 1.1 Critique of the decision problem in the company’s submission ................................ 7 1.2 Summary of the key issues in the clinical effectiveness evidence ........................... 8 1.3 Summary of the key issues in the cost effectiveness evidence ............................. 11 1.4 Summary of ERG’s preferred assumptions and resulting ICER............................. 12 2 INTRODUCTION AND BACKGROUND ....................................................................... 14 2.1 Introduction ........................................................................................................... 14 2.2 Company’s overview of current service provision .................................................. 15 2.3 Ozanimod ............................................................................................................. 18 2.4 Number of patients eligible for treatment with ozanimod ....................................... 19 2.5 Critique of company’s definition of the decision problem ....................................... 19 3 CLINICAL EFFECTIVENESS ....................................................................................... 22 3.1 Systematic review methods .................................................................................. 22 3.2 Identified trials ....................................................................................................... 23 3.3 Characteristics of the included ozanimod trials ..................................................... 24 3.4 Quality assessment for the trials of ozanimod ....................................................... 29 3.5 Statistical approach adopted for the trials of ozanimod ......................................... 30 3.6 Efficacy results from the trials of ozanimod ........................................................... 33 3.7 Patient reported outcomes from the trials of ozanimod ......................................... 37 3.8 Safety and tolerability results from ozanimod studies ............................................ 39 3.9 Safety data for ozanimod versus other relevant comparators ................................ 42 3.10 ERG critique of the indirect evidence .................................................................... 44 3.11 Conclusions of the clinical effectiveness section ................................................... 54 4 COST EFFECTIVENESS ............................................................................................. 56 4.1 Published cost effectiveness evidence .................................................................. 56 4.2 ERG critique of the company’s literature review .................................................... 57 4.3 ERG summary of the company’s submitted economic evaluation ......................... 58 4.4 ERG detailed critique of company economic model .............................................. 73 4.5 Impact on the ICER of additional clinical and economic analyses undertaken by the ERG 79 4.6 Conclusions of the cost effectiveness section ....................................................... 84 5 REFERENCES ............................................................................................................ 85 6 APPENDICES .............................................................................................................. 92 6.1 Appendix 1: other efficacy results from the trials of ozanimod ............................... 92 6.2 Appendix 2: Microsoft Excel revisions made by the ERG to the company’s model 96 Ozanimod for treating relapsing–remitting multiple sclerosis [ID1294] ERG Report Copyright 2021 Queen's Printer and Controller of HMSO. All rights reserved. Page 4 of 98 Confidential until published List of tables Table 1 Current disease modifying treatment options for patients with active RRMS .......................... 17 Table 2 Company estimate of number of patients potentially eligible for treatment with ozanimod in England and Wales in 2019 .................................................................................................................. 19 Table 3 Comparison between NICE scope and company’s decision problem ..................................... 20 Table 4 ERG appraisal of systematic review methods ......................................................................... 22 Table 5 Eligibility criteria for patient entry into the RADIANCE Part A, RADIANCE Part B and SUNBEAM trials .................................................................................................................................... 25 Table 6 Prior treatment and disease activity in the RADIANCE Part B and SUNBEAM trials (pooled data) .....................................................................................................................................................
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