Clinical Issues in Severe Asthma

This activity is provided by Integritas Communications.

This activity is supported by an independent educational grant from Sanofi Genzyme and Regeneron Pharmaceuticals.

A medical education communications company (MECC)-Organized Symposium at the American Thoracic Society (ATS) 2018 International Conference.

All ATS 2018 International Conference attendees are invited to attend this non-CME educational program sponsored by Integritas Communications and supported by a grant from Sanofi Genzyme and Regeneron Pharmaceuticals.

MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

FACULTY FACULTY

Reynold A. Panettieri, Jr, MD Professor of Medicine Robert Wood Johnson Medical School Vice Chancellor, Translational Medicine and Science Director, Rutgers Institute for Translational Medicine and Science New Brunswick, New Jersey Emeritus Professor of Medicine University of Pennsylvania Philadelphia, Pennsylvania Dr. Reynold Panettieri, Jr, is the Director of the Institute for Translational Medicine and Science and Vice Chancellor for Translational Medicine and Science at Rutgers University, and the former Director of the Airways Biology Initiative at the University of Pennsylvania. His interests are in the cellular and molecular mechanisms that regulate airway smooth muscle cell growth and the immunobiology of airway smooth muscle. Consequences of increases in airway smooth muscle growth promote the development of irreversible airflow obstruction and airway remodeling seen in patients with chronic severe asthma. Dr. Panettieri’s lab also focuses on cytosolic signaling pathways that mediate gene expression and alter myocyte function.

Dr. Panettieri also served as the Deputy Director of the Center of Excellence in Environmental Toxicology at the University of Pennsylvania. He directed the human exposure chamber that defines the molecular mechanisms regulating ozone- and particulate matter–induced airway hyperresponsiveness. In parallel with his basic science interests, Dr. Panettieri managed the comprehensive clinical program for the care of patients with asthma and is actively involved in clinical investigations focused on the management of asthma and chronic obstructive pulmonary disease (COPD).

In addition to his research and clinical interests, Dr. Panettieri served as chairperson of the National Institutes of Health (NIH) Lung Cellular, Molecular, and Immunobiology Study Section, is a member of the NIH Distinguished Editorial Panel, and is a member of the American Society for Clinical Investigation and the Association of American Physicians.

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Michael E. Wechsler, MD, MMSc FACULTY

Professor, Department of Medicine Co-Director, The Cohen Family Asthma Institute Division of Pulmonary, Critical Care and Sleep Medicine Director, Asthma Program National Jewish Health Denver, Colorado Dr. Michael Wechsler is Professor of Medicine, Director of the National Jewish Health (NJH)/Cohen Family Asthma Institute. He is also Director of the Asthma Program in the Division of Pulmonary, Critical Care and Sleep Medicine at NJH. He is a member of the Steering Committee and site Principal Investigator of the NIH-sponsored Asthma Clinical Research Network (ACRN, now called AsthmaNet), a multicenter asthma clinical trials consortium, and of the Precision Intervention in Severe/Exacerbating Asthma (PRECISE) network. A member of the American Society of Clinical Investigation, he has participated in many different task forces related to the study of eosinophilic lung diseases that were sponsored by the NIH, the US Food and Drug Administration, the European Respiratory Society, and the International Eosinophil Society.

Professor Wechsler’s research focuses on clinical and translational asthma with emphasis on clinical trials in asthma, novel asthma therapies, bronchial thermoplasty, asthma pharmacogenomics, and management of eosinophilic granulomatosis with polyangiitis (Churg-Strauss Syndrome, CSS). He has led studies focusing on novel biologic agents for asthma and related diseases, including benralizumab, dupilumab, mepolizumab, and reslizumab. He has published more than 170 peer-reviewed manuscripts relating to asthma, CSS, and eosinophilic lung diseases. Professor Wechsler serves as Associate Editor of the journal Allergy and is on the editorial board of the European Journal of Clinical Investigation. Dr. Wechsler received AB and MMSc degrees from Harvard University in Boston, Massachusetts, and his medical degree from McGill University in Montreal, Canada.

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Sally E. Wenzel, MD FACULTY

Professor of Medicine and Immunology Director, University of Pittsburgh Asthma Institute at UPMC/UPSOM UPMC Chair of Translational Airway Biology Chair, Department of Environmental and Occupational Health Graduate School of Public Health University of Pittsburgh Pittsburgh, Pennsylvania Dr. Sally Wenzel completed her medical degree at the University of Florida.

Following her residency in internal medicine at Wake Forest University and her fellowship in pulmonary and critical care medicine at Virginia Commonwealth University, she spent 19 years at National Jewish and the University of Colorado before moving to the University of Pittsburgh. She received the Elizabeth Rich Award for her role in promoting women in science, the ATS Award for Scientific Achievement, the ATS Foundation Breathing for Life Award, and the ERS President’s Award. She is currently Director of the University of Pittsburgh Asthma Institute at UPMC and Chair of the Department of Environmental and Occupational Health at the Graduate School of Public Health, University of Pittsburgh. Dr. Wenzel has served as Deputy Editor for the American Journal of Respiratory and Critical Care Medicine and is a frequent reviewer for The New England Journal of Medicine and other publications.

Dr. Wenzel has a passion for understanding and improving the treatment of asthma, in particular severe asthma. She has promoted severe asthma as a complex disease and her studies of asthma phenotypes have led the field in understanding these complexities. Dr. Wenzel has developed a strong translational program to study the pathobiology of severe asthma and its phenotypes, modeling ex vivo findings in vitro, using primary human airway cells from patients and controls.

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TARGET AUDIENCE The educational design of this activity addresses the needs of allergists/ clinical immunologists, pulmonologists, and other clinicians involved in the management of patients with severe asthma.

EDUCATIONAL OBJECTIVES

PREAMBLE

Upon completion of this activity, participants should be better able to do the following: • Discuss severe asthma heterogeneity and disease biomarkers with a focus on Th2 cell–mediated pathophysiologic mechanisms • Evaluate patients with severe asthma for symptom severity, exacerbation history, comorbidities, disease phenotypes, and prior treatment responses • Differentiate the clinical profiles of current and emerging biologic medications for patients with severe asthma • Individualize therapeutic regimens for patients with severe asthma based on disease phenotypes, ongoing assessment of symptoms, exacerbation risks, and comorbid conditions

STATEMENT OF NEED/PROGRAM OVERVIEW An outsized proportion of asthma-related morbidity and mortality is borne by the 5% to 15% of affected patients who have severe forms of the disease.1,2 These patients suffer from poorly controlled symptoms and frequent exacerbations, often despite daily treatment with high-dose inhaled corticosteroids and other long-acting controller medications.1,2 Ongoing research has elucidated key pathophysiologic processes and other clinical parameters related to asthma severity and persistence.2,3 In many cases, the patient’s medical history, clinical presentation, and results from biomarker testing can help classify severe asthma phenotypically.2,3 Increasingly, this can allow physicians to personalize maintenance regimens using targeted therapies that reflect identified endotypes—ie, asthma phenotypes linked to specific underlying disease mechanisms and proinflammatory signaling cascades.2,4,5 Several biologic medications are now available to treat certain cohorts with severe asthma, and a number of other targeted agents are in late-stage development.5-7 Pulmonologists and other asthma specialists who manage patients with severe asthma need to stay current on the latest published trial data for newer targeted therapies, approvals from the US Food and Drug Administration, and actionable best-practice recommendations on evaluating

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and treating patients with severe asthma. During this Clinical Issues™ program, a panel of expert faculty will discuss and debate a series of topics related to comprehensively evaluating and longitudinally managing patients with severe asthma, including how the evolving evidence base should shape clinical decision-making and implications of new study data presented at the 2018 American Thoracic Society International Conference.

REFERENCES 1. Levy ML. The national review of asthma deaths: what did we learn and what needs to change? Breathe (Sheff). 2015;11(1):14-24.

3. Wan XC, Woodruff PG. Biomarkers in severe asthma. Immunol Allergy Clin North Am. 2016;36(3):547-557.

4. Lötvall J, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127(2):355-360.

5. Fajt ML, Wenzel SE. Asthma phenotypes and the use of biologic medications in asthma and allergic disease: the next steps toward personalized care. J Allergy Clin Immunol. 2015;135(2):299-310.

6. Bousquet J, et al. Care pathways for the selection of a biologic in severe asthma. Eur Respir J. 2017;50(6):1701782.

7. Walsh GM. Biologics targeting IL-5, IL-4 or IL-13 for the treatment of asthma—an update. Expert Rev Clin Immunol. 2017;13(2):143-149.

PROGRAM AGENDA 6:30 pm – 7:00 pm

Registration and Introductions

7:00 pm – 7:15 pm Severe Asthma: Pathophysiology, Heterogeneity, and Burdens 7:15 pm – 7:45 pm Patient Evaluations: Biomarkers, Phenotypes, and Comorbidities 7:45 pm – 8:15 pm Targeted Biologic Therapies for Severe Asthma 8:15 pm – 8:45 pm Personalizing Asthma Management: Case Studies and Patient Perspectives 8:45 pm – 9:00 pm

Question and Answer Session

DISCLOSURE OF CONFLICTS OF INTEREST It is the policy of Integritas Communications that all faculty, instructors, and planners disclose any real or apparent conflicts of interest relating to the topics of this educational activity.

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PREAMBLE

2. Chung KF, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma.

Eur Respir J. 2014;43(2):343-373.

The faculty reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this activity:

PREAMBLE

Reynold A. Panettieri, Jr, MD Speakers Bureau: AstraZeneca; Boehringer-Ingelheim; Boston Scientific Corporation; MedImmune, LLC; Novartis Pharmaceuticals Corporation; Teva Pharmaceutical Industries Ltd; Consultant/Advisor: AstraZeneca; MedImmune, LLC; Novartis Pharmaceuticals Corporation; Research Grant: Amgen Inc.; AstraZeneca; Bristol-Myers Squibb Company; Genentech, Inc.; Gilead Sciences, Inc.; MedImmune, LLC; Novartis Pharmaceuticals Corporation; OncoArendi Therapeutics SA; RFIM; sanofiaventis U.S. LLC; Theratrophix, LLC; Vertex Pharmaceuticals Incorporated Michael E. Wechsler, MD, MMSc Consultant/Advisor: AstraZeneca; Boehringer-Ingelheim; GlaxoSmithKline; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals, Inc.; sanofi-aventis U.S. LLC; Teva Pharmaceutical Industries Ltd. Sally E. Wenzel, MD Consultant, advisor: AstraZeneca; Merck & Co., Inc.; sanofi-aventis U.S. LLC; Research Grant: AstraZeneca; Boehringer-Ingelheim; GlaxoSmithKline; Novartis Pharmaceuticals Corporation; sanofi-aventis U.S. LLC

Non-faculty Rose O’Connor, PhD, CHCP, and Jim Kappler, PhD, hereby state that neither they nor their spouses/life partners have any financial relationships to products or devices with any commercial interest related to the content of this activity of any amount during the past 12 months.

PROVIDER STATEMENT This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through providership of Integritas Communications.

DISCLOSURE OF UNLABELED USE This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the US Food and Drug Administration. Integritas Communications and Sanofi Genzyme and Regeneron Pharmaceuticals do not recommend the use of any agent outside of the labeled indications.

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DISCLAIMER

PREAMBLE

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

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CLINICAL PRACTICE GUIDELINES »»Global Strategy for Asthma Management and Prevention Global Initiative for Asthma (GINA) 2018. http://ginasthma.org/gina-reports

»»International ERS/ATS Guidelines on Definition, Evaluation and Treatment of Severe Asthma Chung KF, et al. Eur Respir J. 2014;43(2):343-373. http://erj.ersjournals.com/content/erj/43/2/343.full.pdf

»»An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FeNO) for clinical applications.

Dweik RA, et al. Am J Respir Crit Care Med. 2011;184(5):602-615. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408724/pdf/ rccm.9120-11ST.pdf

PATIENT RESOURCES »»Asthma and Allergy Foundation of America (AAFA) AAFA is dedicated to improving the quality of life for people with asthma and allergic diseases through education, advocacy, and research. http://www.aafa.org/page/asthma.aspx

»»American College of Allergy, Asthma & Immunology (ACAAI)

RESOURCE CENTER

The ACAAI fosters a culture of collaboration and congeniality in which members work toward the common goals of patient care, education, advocacy, and research. http://acaai.org/

»»American Lung Association The American Lung Association is the leading organization working to save lives by improving lung health and preventing lung disease through education, advocacy, and research. http://www.lung.org/lung-health-and-diseases/lung-diseaselookup/asthma/

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»»American Thoracic Society (ATS) The mission of the ATS is to improve health worldwide by advancing research, clinical care, and public health in respiratory disease, critical illness, and sleep disorders. https://www.thoracic.org/patients/patient-resources/

»»Asthma Action Plan This printable reference tool is designed to help patients know when to use their different asthma medications and when to call their health care providers. http://www.aafa.org/media/asthma-action-plan-aafa.pdf

CLINICAL ASSESSMENT TOOLS »»Asthma Control Test (ACT) This 5-question test evaluates asthma control over the past 4 weeks on a 5-point Likert scale. A score of <20 on the ACT suggests asthma that is uncontrolled.

Nathan RA, et al. J Allergy Clin Immunol. 2004;113(1):59-65. https://www.nhp.org/provider/asthma/Survey–ACT– adult–EN.pdf

»»Asthma Control Questionnaire (ACQ) This 7-question assessment tool measures asthma control over the past 7 days. Six questions are self-administered by the patient, and 1 question requires a clinician’s input. Scores range from 1 (totally controlled) to 6 (severely uncontrolled).

Juniper EF, et al. Eur Respir J. 1999;14(4):902-907. http://www.qoltech.co.uk/acq.html

»»Asthma Therapy Assessment Questionnaire (ATAQ)

RESOURCE CENTER

This 4-question test assesses asthma control over the past 4 weeks. Each question has a possible score of 0 or 1; if the sum of the 4 question scores is >1, the patient’s asthma may be uncontrolled.

Vollmer WM, et al. Am J Respir Crit Care Med. 1999;160(5 Pt 1):1647-1652. http://getasthmahelp.org/documents/2007Guidelines– ValidatedQuestionnaires.pdf

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SUGGESTED READINGS »»American Thoracic Society International Conference Asthma Posters and Oral Sessions. May 18-23, 2018. San Diego, California. http://www.abstractsonline.com/pp8/#!/4499/sessions/@topic1theme=03.%20 Asthma/1

»»Care pathways for the selection of a biologic in severe asthma.

Bousquet J, et al. Eur Respir J. 2017;50(6):1701782. http://erj.ersjournals.com/content/erj/50/6/1701782.full.pdf

»»Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and longacting β2-agonists (SIROCCO): a randomised, multicentre, placebocontrolled phase 3 trial.

Bleecker ER, et al. Lancet. 2016;388(10056):2115-2127. https://www.ncbi.nlm.nih.gov/pubmed/27609408

»»Liberty Asthma QUEST: phase 3 randomized, double-blind, placebocontrolled, parallel-group study to evaluate dupilumab efficacy/ safety in patients with uncontrolled, moderate-to-severe asthma.

Busse WW, et al. Adv Ther. May 2018 [Epub Ahead of Print]. https://link.springer.com/content/pdf/10.1007%2Fs12325-018-0702-4.pdf

»»A randomized, controlled phase 3 study, LIBERTY ASTHMA QUEST, evaluating the efficacy and safety of dupilumab in uncontrolled moderate-to-severe asthma.

RESOURCE CENTER

Castro M, et al. American Thoracic Society International Conference. May 18-23, 2018. San Diego, California. Presentation Session A101. Presentation A7700. http://www.abstractsonline.com/pp8/#!/4499/presentation/22020

»»Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, doubleblind, randomised, placebo-controlled, phase 3 trials.

Castro M, et al. Lancet Respir Med. 2015;3(5):355-366. https://www.ncbi.nlm.nih.gov/pubmed/25736990

»»Tezepelumab in adults with uncontrolled asthma.

Corren J, et al. N Engl J Med. 2017;377(10):936-946. https://www.ncbi.nlm.nih.gov/pubmed/?term=28877011

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»»A review of anti-IgE monoclonal antibody (omalizumab) as add on therapy for severe allergic (IgE-mediated) asthma.

D’Amato G, et al. Ther Clin Risk Manag. 2007;3(4):613-619. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374942/pdf/tcrm-0304-613.pdf

»»Inflammatory and comorbid features of patients with severe asthma and frequent exacerbations.

Denlinger LC, et al. Am J Respir Crit Care Med. 2017;195(3):302-313. https://www.ncbi.nlm.nih.gov/pubmed/?term=27556234

»»Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial.

Gonem S, et al. Lancet Respir Med. 2016;4(9):699-707. https://www.ncbi.nlm.nih.gov/pubmed/?term=27503237

»»Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebocontrolled phase 3 trial.

FitzGerald JM, et al. Lancet. 2016;388(10056):2128-2141. https://www.ncbi.nlm.nih.gov/pubmed/27609406

»»Severe and difficult-to-treat asthma in adults.

Israel E, Reddel HK. N Engl J Med. 2017;377(10):965-976. http://www.nejm.org/doi/pdf/10.1056/NEJMra1608969

Kim MA, et al. Curr Opin Allergy Clin Immunol. 2014;14(1):49-54. https://www.ncbi.nlm.nih.gov/pubmed/24300416

»»Mepolizumab treatment in patients with severe eosinophilic asthma.

Ortega HG, et al. N Engl J Med. 2014;371(13):1198-1207. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1403290

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RESOURCE CENTER

»»Adult asthma biomarkers.

»»Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies.

Ortega HG, et al. Lancet Respir Med. 2016;4(7):549-556. https://www.ncbi.nlm.nih.gov/pubmed/?term=27177493

»»Allergen immunotherapy in asthma; what is new?

Passalacqua G, et al. Asthma Res Pract. 2015;1:6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970380/pdf/40733 –2015 – Article – 6.pdf

»»Co-morbidities in severe asthma: clinical impact and management.

Porsbjerg C, Menzies-Gow, A. Respirology. 2017;22(4):651-661. http://onlinelibrary.wiley.com/doi/10.1111/resp.13026/epdf

»»Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebocontrolled pivotal phase 2b dose-ranging trial.

RESOURCE CENTER

Wenzel S, et al. Lancet. 2016;388(10039):31-44. https://www.ncbi.nlm.nih.gov/pubmed/27130691

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