Atrial Fibrillation (Event Driven)

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1 Brochure More information from Atrial Fibrillation (Event Driven) Description: Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice. The disease poses a major public health and financial burden, and it remains an area of significant unmet need in terms of both preventing and treating the arrhythmia itself as well as its main complication: stroke. Furthermore, the opportunity for therapies that reduce stroke and agents that can maintain regular heart rhythm is expanding because of an aging population and growing awareness of the limitations of existing AF drugs. New drugs in development stand to fundamentally alter treatment patterns, reduce the burden of AF, and dramatically improve patient outcomes. Contents: Executive Summary What are the key parameters of the atrial fibrillation market? What factors are driving the market for atrial fibrillation therapies? What factors are constraining the market for atrial fibrillation therapies? What are the drug development activities of note in atrial fibrillation? What do the experts say? What key challenges and opportunities remain? 1 Etiology and Pathophysiology Disease Pathophysiology Natural History and Risk Factors The Fibrillating Heart Ion Channels and Gap Junctions The Cardiac Action Potential Substrate Remodeling Inflammatory Factors Contributing to Atrial Fibrillation Electrical Remodeling Structural Remodeling The Role of Genetics in Atrial Fibrillation Induction Triggering Factors in AF The Single-Focus Hypothesis Multiple-Wavelet Hypothesis The Pulmonary Vein and Initiation of Atrial Fibrillation Thromboembolism in Atrial Fibrillation Pathways and Drug Targets Novel Antiarrhythmic Drug Targets The SK2 Ion Channel Atrial-Selective Potassium Channels Mitochondrial Drug Targets Heat Shock Proteins MicroRNAs as Novel Therapeutic Targets for AF Novel Drug Targets to Inhibit Atrial Fibrosis Antithrombotic Drug Targets 2 Epidemiology and Patient Populations Disease Definition Methods Diagnosed Prevalent Cases Acute Events Subpopulations Diagnosed and Drug-Treated Populations Percentage Diagnosed Percentage Drug-Treated

2 3 Current Therapies and Medical Practice Treatment Providers Goals of Treatment Currently Marketed Products Antiarrhythmic Drugs for Maintaining Sinus Rhythm Class I Antiarrhythmic Drugs Class III Antiarrhythmic Drugs Dronedarone Antiarrhythmic Drugs for Maintaining Sinus Rhythm: Prescription Trends Antiarrhythmic Drugs for AF Cardioversion Vernakalant Rate-Control Drugs Anticoagulants Warfarin Dabigatran Etexilate Rivaroxaban Treatment Guidelines and Factors Influencing Drug Selection Treatment Algorithm Atrial Fibrillation Cardioversion Country-Specific Prescribing Practices Country-Specific Reimbursement Issues Nonpharmacological Treatment Approaches 4 Unmet Needs Efficacious Antiarrhythmics Without Proarrhythmic Side Effects Fixed-Dose Oral Anticoagulants to Replace Vitamin K Antagonists Reduction of Morbidity and Mortality in Patients with Atrial Fibrillation and Chronic Heart Failure Antidotes for Emerging Oral Anticoagulants Primary Prevention of Atrial Fibrillation Further Understanding of Atrial Fibrillation Pathophysiology to Indentify Individualized Treatment Strategies and Novel Drug Targets 5 Emerging Therapies Future Positioning of Key Competitors Drug Development and Regulatory Hurdles Early-Stage Therapies Heat Shock Protein Inducers SK2 Channel Inhibitors Other Novel Atrial Fibrillation Drugs Anticoagulants Apixaban Edoxaban Betrixaban Darexaban Tecarfarin Atrial Selective Antiarrhythmics Vernakalant Class III Antiarrhythmics Ranolazine Budiodarone K-201 Celivarone Specific Ultra-Rapid Potassium-Channel Antagonists

3 XEN-D0103 Specific Acetylcholine-Activated Potassium-Channel Antagonists NTC-801 XEN-R0702 Gap Junction Modulators Danegaptide Adenosine A1 Receptor Agonists Renin-Angiotensin-Aldosterone System Inhibitors Irbesartan Olmesartan 6 Market Outlook Drug-Class-Specific Trends Anticoagulants Class IA Antiarrhythmics Class IC Antiarrhythmics Class III Antiarrhythmics Atrial-Selective Antiarrhythmics Beta Blockers Calcium-Channel Blockers Cardiac Glycosides Alternative Market Scenarios Appendix A Bibliography Atrial Fibrillation Appendix B Market Forecast Methodology Bottom-Up Market Forecasting Patient Populations Drug-Specific Assumptions General Sources of Data Pricing, Dosing, Days of Therapy, and Compliance Assumptions General Statements About Pricing Dosing, Days of Therapy and Compliance Generic Erosion Emerging Therapy Prices Appendix C Experts Interviewed Atrial Fibrillation Appendix D Supplemental Epidemiology Bibliography Tables and Figures Table 2-1 Number of Diagnosed Prevalent Cases of Atrial Fibrillation in the Major Pharmaceutical Markets, Table 2-2 Number of Diagnosed Prevalent Cases of Atrial Fibrillation in the Major Pharmaceutical Markets by Subtype, Table 2-3 Number of Diagnosed Events of Atrial Fibrillation in the Major Pharmaceutical Markets by Event Type, Table 2-4 Number of Diagnosed and Drug-Treated Prevalent Cases of Paroxysmal Atrial Fibrillation in the Major Pharmaceutical Markets, Table 2-5 Number of Diagnosed and Drug-Treated Prevalent Cases of Persistent Atrial Fibrillation in the

4 Major Pharmaceutical Markets, Table 2-6 Number of Diagnosed and Drug-Treated Prevalent Cases of Permanent Atrial Fibrillation in the Major Pharmaceutical Markets, Table 2-7 Number of Diagnosed Prevalent Cases of Atrial Fibrillation in the Major Pharmaceutical Markets by Heart Failure Status, Table 2-8 Number of Diagnosed Prevalent Cases of Atrial Fibrillation in the Major Pharmaceutical Markets by CHADS2 Score, Table 2-9 Number of Total Prevalent Cases of Atrial Fibrillation in the Major Pharmaceutical Markets by Hypertension Status, Table 2-10 Key Sources for Atrial Fibrillation Epidemiology and Model Parameters Table 3-1 Atrial Fibrillation Treatment Providers and Referral Patterns by Market Table 3-2 End Points Used in Clinical Trials for Atrial Fibrillation Table 3-3 Leading Current Therapies Used for Atrial Fibrillation, 2010 Table 3-4 Current Classes Used for Atrial Fibrillation Table 3-5 Current Therapies Used for Atrial Fibrillation Table 3-6 Comparison of Current Therapies for Atrial Fibrillation Table 3-7 Efficacy of Key Therapies for Cardioversion in Atrial Fibrillation Table 3-8 Efficacy of Key Therapies for Maintenance of Sinus Rhythm in Atrial Fibrillation Table 3-9 Expert Insight on Select Current Antiarrhythmic Drugs Table 3-10 Atrial Fibrillation Treatment Guidelines by Market Table 3-11 Factors Influencing Drug Selection in Atrial Fibrillation Table 3-12 Expert Insight on Common Clinical Strategies for Atrial Fibrillation Cardioversion Table 3-13 Prescribing Practices by Market Table 3-14 Reimbursement Environment for Atrial Fibrillation by Market Table 5-1 Emerging Therapies in Development for Atrial Fibrillation Table 5-2 Estimated Launch Dates for Key Emerging Therapies for the Treatment of Atrial Fibrillation Table 6-1 Sales of Drugs to Treat Atrial Fibrillation (All Populations) in the Major Pharmaceutical Markets, Table 6-2 Timeline of Key Market Events for Atrial Fibrillation Table 6-3 Alternative Market Scenarios for the Atrial Fibrillation Market Through 2020 Table B-1 Sources for Drug Prices Figure 1-1 Classification of Atrial Fibrillation Figure 1-2 The Cardiac Conduction System Figure 1-3 Comparison of ECG Recordings from Healthy and AF Patients

5 Figure 1-4 Phases and Ionic Currents of the Human Cardiac Action Potential Figure 1-5 Ion-Channel Expression Changes in Human Atrial Fibrillation Figure 1-6 Antithrombotic Drug Targets Figure 2-1 Total Diagnosed Prevalence and Total Diagnosed Prevalent Cases of Atrial Fibrillation in the Major Markets, 2010 Figure 3-1 Reasons Underlying the Use of Leading Oral Antiarrhythmic Drugs in 2010 Figure 3-2 Pharmacological Management of Patients with Recurrent Paroxysmal Atrial Fibrillation Figure 3-3 Pharmacological Management of Patients with Recurrent Persistent and Permanent Atrial Fibrillation Figure 3-4 Treatment Algorithm for Maintenance of Normal Sinus Rhythm in Patients with Recurrent Paroxysmal or Persistent Atrial Fibrillation Figure 3-5 Treatment Algorithm for Antithrombotic Therapy for Stroke Prevention in Atrial Fibrillation Figure 4-1 Unmet Needs: Attainment and Remaining Opportunity in Atrial Fibrillation Figure 4-2 Theoretical Pharmacodynamic Scenarios for Novel Oral Anticoagulants and an Intravenous Antidote Figure 6-1 Atrial Fibrillation Therapies, Market Share Figure 6-2 Timeline of Near-Term Events in Atrial Fibrillation Ordering: Order Online - Order by Fax - using the form below Order by Post - print the order form below and send to Research and Markets, Guinness Centre, Taylors Lane, Dublin 8, Ireland.

6 Page 1 of 2 Fax Order Form To place an order via fax simply print this form, fill in the information below and fax the completed form to (from USA) or (from Rest of World). If you have any questions please visit Order Information Please verify that the product information is correct. Product Name: Web Address: Office Code: Atrial Fibrillation (Event Driven) SC Product Format Please select the product format and quantity you require: Electronic - Single User: Quantity USD Contact Information Please enter all the information below in BLOCK CAPITALS Title: Mr Mrs Dr Miss Ms Prof First Name: Last Name: Address: * Job Title: Organisation: Address: City: Postal / Zip Code: Country: Phone Number: Fax Number: * Please refrain from using free accounts when ordering (e.g. Yahoo, Hotmail, AOL)

7 Page 2 of 2 Payment Information Please indicate the payment method you would like to use by selecting the appropriate box. Pay by credit card: You will receive an with a link to a secure webpage to enter your credit card details. Pay by check: Please post the check, accompanied by this form, to: Research and Markets, Guinness Center, Taylors Lane, Dublin 8, Ireland. Pay by wire transfer: Please transfer funds to: Account number Sort code Swift code IBAN number Bank Address ULSBIE2D IE78ULSB Ulster Bank, Main Street, Blackrock, Co. Dublin, Ireland. If you have a Marketing Code please enter it below: Marketing Code: Please note that by ordering from Research and Markets you are agreeing to our Terms and Conditions at Please fax this form to: (646) or (646) From USA or From Rest of World

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