Deflazacort, Eteplirsen, and Golodirsen for Duchenne Muscular Dystrophy: Effectiveness and Value Final Evidence Report August 15, 2019 Prepared for ©Institute for Clinical and Economic Review, 2019 University of Illinois at Chicago College of Pharmacy ICER Staff and Consultants Modeling Group Grace A. Lin, MD Catherine Koola, MPH Surrey M. Walton, PhD Associate Professor of Program Manager Associate Professor, Pharmacy Systems, Outcomes and Policy Medicine and Health Policy ICER Assistant Director, Center for Pharmacoepidemiology and University of California, San Pharmacoeconomic Research Francisco University of Illinois at Chicago College of Pharmacy Foluso Agboola, MBBS, MPH Matt Seidner Nicole Boyer, PhD Director, Evidence Synthesis Program Director Postdoctoral Fellow ICER ICER The University of Chicago Noemi Fluetsch, MPH Rick Chapman, PhD, MS Danny Quach, PharmD Research Assistant, Health Director of Health Economics University of Illinois at Chicago College of Pharmacy Economics and Outcomes ICER Research ICER Varun M. Kumar, MBBS, MPH, David Rind, MD, MSc MSc Chief Medical Officer Associate Director of Health ICER Economics ICER The role of the University of Illinois (UIC) College of Pharmacy Sumeyye Samur, PhD, MS Steve Pearson, MD, MSc Modeling Group is limited to the development of the cost- Health Economist President effectiveness model, and the resulting ICER reports do not ICER ICER necessarily represent the views of the UIC. DATE OF PUBLICATION: August 15, 2019 Grace Lin served as the lead author for the report and wrote the background, other benefits, and contextual considerations sections of the report. Foluso Agboola was responsible for the oversight of the systematic review and authorship of the comparative clinical effectiveness section with the support of Ifeoma Otuonye and Noemi Fluetsch. Varun Kumar and Sumeyye Samur were responsible for oversight of the cost-effectiveness analyses and Sumeyye Samur developed the budget impact model. Catherine Koola authored the section on coverage policies and clinical guidelines. Surrey Walton, Nicole Boyer, and Danny Quach developed the cost-effectiveness model and authored the corresponding sections of the report. David Rind, Rick Chapman, and Steven Pearson provided methodologic guidance on the clinical and economic evaluations. We would also like to thank Laura Cianciolo and Maggie O’Grady for their contributions to this report. ©Institute for Clinical and Economic Review, 2019 Page ii Final Evidence Report – Deflazacort, Eteplirsen, and Golodirsen for DMD About ICER The Institute for Clinical and Economic Review (ICER) is an independent non-profit research organization that evaluates medical evidence and convenes public deliberative bodies to help stakeholders interpret and apply evidence to improve patient outcomes and control costs. Through all its work, ICER seeks to help create a future in which collaborative efforts to move evidence into action provide the foundation for a more effective, efficient, and just health care system. More information about ICER is available at http://www.icer-review.org. The funding for this report comes from government grants and non-profit foundations, with the largest single funder being the Laura and John Arnold Foundation. No funding for this work comes from health insurers, pharmacy benefit managers, or life science companies. ICER receives approximately 19% of its overall revenue from these health industry organizations to run a separate Policy Summit program, with funding approximately equally split between insurers/PBMs and life science companies. No life science companies relevant to this review participate in this program. For a complete list of funders and for more information on ICER's support, please visit http://www.icer-review.org/about/support/. About the New England CEPAC The New England Comparative Effectiveness Public Advisory Council (New England CEPAC) – a core program of ICER – provides a public venue in which the evidence on the effectiveness and value of health care services can be discussed with the input of all stakeholders. The New England CEPAC seeks to help patients, clinicians, insurers, and policymakers interpret and use evidence to improve the quality and value of health care. The New England CEPAC Council is an independent committee of medical evidence experts from across New England, with a mix of practicing clinicians, methodologists, and leaders in patient engagement and advocacy. All Council members meet strict conflict of interest guidelines and are convened to discuss the evidence summarized in ICER reports and vote on the comparative clinical effectiveness and value of medical interventions. More information about the New England CEPAC is available at https://icer-review.org/programs/new-england-cepac/. ©Institute for Clinical and Economic Review, 2019 Page iii Final Evidence Report – Deflazacort, Eteplirsen, and Golodirsen for DMD The findings contained within this report are current as of the date of publication. Readers should be aware that new evidence may emerge following the publication of this report that could potentially influence the results. ICER may revisit its analyses in a formal update to this report in the future. The economic models used in ICER reports are intended to compare the clinical outcomes, expected costs, and cost-effectiveness of different care pathways for broad groups of patients. Model results therefore represent average findings across patients and should not be presumed to represent the clinical or cost outcomes for any specific patient. In addition, data inputs to ICER models often come from clinical trials; patients in these trials and provider prescribing patterns may differ in real-world practice settings. ©Institute for Clinical and Economic Review, 2019 Page iv Final Evidence Report – Deflazacort, Eteplirsen, and Golodirsen for DMD In the development of this report, ICER’s researchers consulted with several clinical experts, patients, manufacturers, and other stakeholders. The following clinical experts provided input that helped guide the ICER team as we shaped our scope and report. None of these individuals are responsible for the final contents of this report or should be assumed to support any part of this report, which is solely the work of the ICER team and its affiliated researchers. For a complete list of stakeholders from whom we requested input, please visit: https://icer- review.org/material/dmd-stakeholder-list/. Expert Reviewers Emma Ciafaloni, MD Professor of Neurology and Pediatrics University of Rochester Dr. Ciafaloni has received personal compensation for serving on advisory boards and/or as a consultant for Sarepta, Biogen, Santhera, Strongbridge, AveXis, PTC Therapeutics, and Pfizer, and has received research support from MDA, Cure SMA, PPMD, PTC, Sarepta, Santhera, NIH, FDA, CDC, and PCORI. She is a member of the Data Safety Monitoring Board for AveXis gene therapy trials in SMA and serves as chair for the Sarepta Duchenne gene therapy trials. Peter B. Kang, MD Chief, Division of Pediatric Neurology University of Florida College of Medicine Dr. Kang has served as site primary investigator (PI) for a Pfizer study on DMD, as co-investigator for a Catabasis study on DMD, and on a planning committee for a Solid Biosciences study on DMD. He currently serves as a consultant for AveXis and ChromaDex, and has served on advisory boards for Sarepta Therapeutics. He has also received royalties from Springer for co-editing a textbook and from Wolters Kluwer for authorship of topics for UpToDate, and honoraria from Wiley for an editorial role with the journal Muscle & Nerve. ©Institute for Clinical and Economic Review, 2019 Page v Final Evidence Report – Deflazacort, Eteplirsen, and Golodirsen for DMD Table of Contents Executive Summary ............................................................................................................................ ES1 Background .................................................................................................................................... ES1 Comparative Clinical Effectiveness ................................................................................................ ES4 Corticosteroids ............................................................................................................................... ES4 Exon-Skipping Therapies ................................................................................................................ ES7 Long-Term Cost Effectiveness ...................................................................................................... ES10 Potential Other Benefits and Contextual Considerations ............................................................ ES16 Value-Based Price Benchmarks .................................................................................................... ES18 Potential Budget Impact .............................................................................................................. ES18 New England CEPAC Votes ........................................................................................................... ES19 Key Policy Implications ................................................................................................................. ES22 1. Introduction ....................................................................................................................................... 1 1.1 Background .................................................................................................................................