Emicizumab for Hemophilia A with Inhibitors: Effectiveness and Value Evidence Report March 15, 2018 Prepared for ©Institute for Clinical and Economic Review, 2018 University of Washington School of Pharmacy ICER Staff Modeling Group David Rind, MD Lotte Steuten, MSc, PhD Chief Medical Officer University of Washington Institute for Clinical and Economic Review Gregory Guzauskas, MSPH, PhD Foluso Agboola, MBBS, MPH University of Washington Research Scientist Institute for Clinical and Economic Review Varun Kumar, MBBS, MPH, MSc Health Economist Institute for Clinical and Economic Review Celia Segel, MPP Program Manager Institute for Clinical and Economic Review Rick Chapman, PhD, MS Director of Health Economics Institute for Clinical and Economic Review Alexandra Ellis, MSc, AM Senior Scientist, HTA and Economic Evaluation Institute for Clinical and Economic Review Daniel A. Ollendorf, PhD Chief Scientific Officer Institute for Clinical and Economic Review Steven D. Pearson, MD, MSc President Institute for Clinical and Economic Review DATE OF PUBLICATION: March 15, 2018 David Rind served as the lead author for the report. Foluso Agboola led the systematic review and authorship of the comparative clinical effectiveness section. Varun Kumar and Rick Chapman were responsible for oversight of the cost-effectiveness analyses and developed the budget impact model. Celia Segel authored the section on coverage policies and clinical guidelines. Alexandra Ellis, Dan Ollendorf, and Steven Pearson provided methodologic guidance on the clinical and economic evaluations. The role of the University of Washington (UW) School of Pharmacy Modeling Group is limited to the development of the cost-effectiveness model, and the resulting ICER reports do not necessarily represent the views of the UW. We would also like to thank Molly Morgan, Aqsa Mugal, Erin Lawler, and Matt Seidner for their contributions to this report. ©Institute for Clinical and Economic Review, 2018 Page i Evidence Report: Emicizumab for Hemophilia A with Inhibitors 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 20% 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. For a complete list of funders and for more information on ICER's support, please visit http://www.icer-review.org/about/support/. About 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. 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 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 New England CEPAC is available at http://icer-review.org/programs/new-england-cepac/. 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. ©Institute for Clinical and Economic Review, 2018 Page ii Evidence Report: Emicizumab for Hemophilia A with Inhibitors Acknowledgements 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 is 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/hemophilia-stakeholder-list/. Expert Reviewers Steven Pipe, MD Professor of Pediatrics and Communicable Diseases; Professor of Pathology University of Michigan Dr. Pipe has disclosed receipt of consulting fees in excess of $5,000 from the following life sciences companies: Bayer, BioMarin, Bioverativ, CSL Behring, Novo Nordisk, Pfizer, Roche, Shire, uniQure. In addition, Shire has sponsored basic research conducted by Dr. Pipe. Margaret V. Ragni, MD, MPH Professor of Medicine, Division of Hematology/Oncology, University of Pittsburgh; Director, Hemophilia Center of Western PA No relevant conflicts of interest to disclose, defined as more than $10,000 in healthcare company stock or more than $5,000 in honoraria or consultancies during the previous year from health care manufacturers or insurers Mark W. Skinner, JD President and CEO, Institute for Policy Advancement Ltd.; Past President (2004-2012), World Federation of Hemophilia; President, World Federation of Hemophilia USA Mr. Skinner has disclosed the following relationships: • Honoraria > $5,000: Mr. Skinner has received honoraria for educational presentations and advisory board participation with F. Hoffman-La Roche, Bayer Healthcare, and the Blue Cross Blue Shield Medical Advisory Panel. • Equity Interests > $10,000: Mr. Skinner’s household has equity interests in the following companies: CVS, Foundation Medicine, Illumina, Intuitive Surgical, Merck, Novartis, Regeneron. These holdings are managed by a financial advisor with instructions not to invest in companies with a known interest in therapies for bleeding disorders. • Positions: Mr. Skinner is the president of World Federation of Hemophilia USA, which receives product and monetary donations for a humanitarian aid program, serves as a ©Institute for Clinical and Economic Review, 2018 Page iii Evidence Report: Emicizumab for Hemophilia A with Inhibitors consultant for the US National Hemophilia Foundation, and is a member of the NHF Scientific Advisory Council. • Research: Mr. Skinner is a Principal investigator for the Patient-Reported Outcomes and Burdens and Experiences (PROBE) study, which is funded with grant support from Baxalta (part of Shire), Bayer, Bioverativ, CSL Behring, Novo Nordisk, Roche, Sobi. The PROBE study is an independent, investigator-led research project led by patients and patient advocacy organizations. • Personal: Mr. Skinner is a person with severe hemophilia A. ©Institute for Clinical and Economic Review, 2018 Page iv Evidence Report: Emicizumab for Hemophilia A with Inhibitors Return to Table of Contents Table of Contents Executive Summary ............................................................................................................................ ES1 1. Introduction ....................................................................................................................................... 1 1.1 Background .................................................................................................................................. 1 1.2 Scope of the Assessment ............................................................................................................. 7 1.3 Definitions .................................................................................................................................... 9 1.4 Insights Gained from Discussions with Patients and Patient Groups ........................................ 10 1.5 Potential Cost-Saving Measures in Hemophilia ......................................................................... 11 2. Summary of Coverage Policies and Clinical Guidelines ................................................................... 13 2.1 Coverage Policies ....................................................................................................................... 13 2.2 Clinical Guidelines ...................................................................................................................... 14 3. Comparative Clinical Effectiveness .................................................................................................. 16 3.1 Overview .................................................................................................................................... 16 3.2 Methods ....................................................................................................................................