Transcatheter Aortic Valve Replacement Analysis and Market Forecast - US Market GDME1001CFR / Published November 2012
Executive Summary Transcatheter Aortic Valve Replacement: Key Metrics in US Device Markets Diseased population Severe, Symptomatic Population High Risk or Inoperable Population 2011 Market Sales US Pipeline Assessment 1.45 million 0.20 million 0.13 million $28.0m Number of preclinical devices 7 Transcatheter Aortic Valve Market is Forecast to Witness Significant Growth Through 2018 The Transcatheter Aortic Valve Replacement (TAVR) market is forecast to have significant growth during the forecast period. GlobalData estimates the US market in 2011 was $28.0 million, and it is expected to grow to reach $1,086.1 million by 2018. The key drivers for the market in the forecast period are: Number of early clinical devices 4 Number of late clinical devices 3 Pericardium Tissue Valves 87% Synthetic Polymer Valves 13% Key events (2011-2018) US FDA approval of Sapien valve for inoperable patients via transfemoral access in 2011 US FDA expanded approval for high-risk patients via transapical access in 2012 Level of Impact Increase in the TAVR patient population, primarily due to an increase in the elderly population and expanded approval of TAVR US FDA approval of TAVR using Sapien valve in inoperable candidates via transfemoral access in 2011 FDA expanded approval of TAVR for high-risk patients and transapical access in 2012 US FDA approval of CoreValve in 2014 US FDA approval of Acurate TA valve in 2014 US FDA of Sapien XT in 2014 2018 Market Sales US Source: GlobalData $1,086m FDA approval of CoreValve in 2014 FDA approval of Acurate TA valve in 2014 FDA approval of Sapien XT valve in 2014 The major barriers for the TAVR market are: Lacking and incomplete reimbursement for TAVR procedures Slow adoption of TAVR as heart centers are trained in the procedure High cost of current devices compared to surgically implanted valve prosthetics Page 2 GDME1001CFR / Published NOV 2012
Executive Summary Companies Working to Get Their Devices Approved in the TAVR Market The TAVR market has been developing quickly as a result of US rapid adoption of the procedure. Ever since the Sapien valve was approved by the FDA in the US in 2011, additional companies have been working to enter the market as well. TAVR device technology has already entered the next stage of development, with many second-generation prosthetics due to launch in the US in the near future. In parallel development with device designs, companies are looking to further improve their delivery systems as well. Expanded approval of TAVR in the US has generated considerable interest within the healthcare community. GlobalData expects that most major heart centers will offer the procedure in coming years. Significant Unmet Needs in TAVR Market Use of TAVR in high-risk and inoperable patients has proven effective in treating aortic valve disease; however, there is still much room for improvement. Paravalvular regurgitation and a high incidence of stroke have plagued first-generation devices, and emerging products aim to reduce these side effects while also reducing the cost of the device. Additionally, physicians have called for other device improvements, most notably repositionability and reduced delivery sheath sizes. Improvements to the device design will help TAVR be approved for moderate and low surgical risk patients by improving patient outcomes, reducing device cost, and making TAVR superior to surgical valve replacement. Remaining Opportunities for New Entrants Significant market opportunities still exist for novel TAVR devices in terms of superior efficacy, improved ease of use, lower adverse effects, and cost. There have been numerous design adaptations across the TAVR industry as companies look to differentiate their product from the competition. Compared to the first TAVR products approved, many second-generation devices are smaller in profile size as well as repositionable. Looking ahead, others including Direct Flow Medical and AorTech International are working to develop devices with prosthetic valve leaflets made of synthetic polymers in an attempt to improve durability and reduce the device cost. Also working towards improved durability, ValveXchange has developed a TAVR system with exchangeable leaflets that can be replaced as they wear out. In an attempt to reduce regurgitation, Boston Scientific and Symetis are both developing valves that utilize sealing membrane skirts to increase prosthetic conformance to the native valve annulus and reduce paravalvular regurgitation. Most device improvements have been related to accurate positioning of the prosthetic, secure anchoring, improved durability, ease of deployment and cost. As more companies enter the market, these points of difference between various TAVR products are likely to drive sales. Leading TAVR Companies and Future Landscape Edwards is the only company with a device currently approved in the US. As the US market opens up to other competitors, GlobalData believes the TAVR market will continue to grow rapidly in the near term. Additionally, several medical device giants have still not developed their own TAVR technologies, and so GlobalData expects significant merger and acquisition activity within the TAVR market. New players entering the market will combat initial challenges with physician adoption as a result of the retraining necessary for new TAVR devices; each prosthetic behaves differently. The market is still very young, though, and there is great potential for new entrants with superior efficacy, lower costs, or both. Page 3 GDME1001CFR / Published NOV 2012
Executive Summary Assessment of TAVR Device Features Most Desirable Features of TAVR Devices Features Most Satisfied With (Met Needs) Features Least Satisfied With (Unmet Needs) Source: GlobalData What do Physicians Think? Repositionability High durability and long device lifetime Proven safety of device Non-thrombogenic Dynamic responsiveness Valve-tissue interaction Cost of device Retrievability of device Self-repairing ability of device Physicians feel strongly that TAVR adoption will be strong in coming years. I think that most patients are probably going to go for transcatheter valves once the newer technology is available TAVR is going to explode. It s going to be THE valve platform in ten years, I mean, nobody s going to be doing open valve anymore. Key Opinion Leader, October 2012 were otherwise operated on will in the future be treated with transcatheter heart valves. Key Opinion Leader, October 2012 While TAVR is currently only approved for high-risk and inoperable patients, it is likely that moderate and low-risk patients will be candidates for TAVR in the future. We already, more or less, are convinced that lower risk patients may benefit from a transcatheter heart valve. So, we re already shifting to these lower risk patients. Key Opinion Leader, October 2012 But before TAVR is approved for lower risk patients, many are calling for further improvement. Limitations have to be addressed before offering TAVR to lower risk patients...so maybe in a short time, maybe five years, the surgical-risk requirement for TAVR will go down. Key Opinion Leader, November 2012 While adoption of TAVR in the US has been slower than in Europe, many believe the approval of second generation devices will boost sales. While physicians are calling for numerous device improvements, two attributes are of particular importance. Once the FDA approves the smaller devices, you will see a big increase in the number of implants in the US and also the number of approaches. Key Opinion Leader, October 2012 From a patient standpoint, the procedure and recovery time for TAVR is much less compared with The two most important things will be the development of more predictable devices with fewer complications, and the price of the valves going down. If these two things happen, the numbers will further increase. Key Opinion Leader, November 2012 conventional surgical valve replacement. Transcatheter procedures take two hours instead of the usual four or five hours [with surgical implantation] we re shifting, and more patients that Page 4 GDME1001CFR / Published NOV 2012
1 Table of Contents 1 Table of Contents...5 1.1 List of Tables...11 1.2 List of Figures...14 2 Introduction...15 2.1 Catalyst...15 3 Disease Overview...16 3.1 Anatomy & Physiology...16 3.1.1 Heart Valves...16 3.2 Pathophysiology...18 3.2.1 Heart Valve Disorders...18 3.2.2 Etiology of AVD...19 3.2.3 Acquired Disorders...19 3.2.4 Congenital Defects...21 3.2.5 Other Disorders...22 3.3 Clinical Presentation...22 3.3.1 Symptoms...22 3.3.2 Diagnosis...22 3.4 Clinical Outcomes...26 3.4.1 Treatment Modalities...27 3.4.2 Medication...30 3.4.3 Heart Valve Repair...31 3.4.4 Surgical/Intervention Strategies...32 3.4.5 Surgical Heart Valve Replacement...32 3.4.6 Transcatheter Heart Valve Replacement...34 3.4.7 Associated Mortality...37 3.5 Epidemiology...37 Page 5 GDME1001CFR / Published NOV 2012
3.5.1 Prevalence...37 3.5.2 Treatment and Mortality...39 3.6 Economic Impact...41 3.6.1 Individual Costs...42 3.6.2 Industry Costs...43 4 Competitive Assessment...44 4.1 Overview...44 4.1.1 Initial Devices...45 4.1.2 Current Devices...45 4.1.3 Competitive Assessment...46 4.2 US Marketed Product Profile...47 4.2.1 Sapien valve (Edwards Lifesciences)...47 5 Unmet Needs...50 5.1 Delivery & Implantation...51 5.1.1 Repositionable...51 5.1.2 Low Profile...51 5.1.3 Accurate Anatomic Positioning...52 5.1.4 Expansion Mechanism...53 5.1.5 Rapid Pacing...53 5.1.6 Motorized Delivery Systems...53 5.1.7 Coronary Ostia Impairment...54 5.2 Conformance...54 5.2.1 Regurgitation...54 5.2.2 Sizing...55 5.2.3 Effective Orifice Area...55 5.2.4 Removal of Native Valve Leaflets...55 5.3 Lifetime...56 5.3.1 Durability...56 5.3.2 Retrievability...57 Page 6 GDME1001CFR / Published NOV 2012
5.3.3 Pacemaker Placement (heart block)...57 5.3.4 Replaceable Leaflets...57 5.4 Materials...58 5.4.1 Alternative Surfaces...58 5.4.2 Endothelialization...58 5.4.3 Regenerative Medicine...59 5.4.4 Tailored Treatment...59 5.5 Pre-Crimped Packaging...59 5.6 Embolic Protection...59 5.7 Robotic Assistance...60 5.8 Hemodynamic Performance...60 6 Pipeline Products...61 6.1 Overview...61 6.2 Pipeline by Phases in Development...62 6.3 Pipeline Products Profiles...64 6.3.1 Acurate TA Valve (Symetis)...64 6.3.2 Acurate TF valve (Symetis)...65 6.3.3 AorTech valve (AorTech International)...67 6.3.4 AorTx valve (Hansen Medical)...68 6.3.5 Centera valve (Edwards Lifesciences)...70 6.3.6 Colibri valve (Colibri Heart Valve)...71 6.3.7 Cormove (Perouse Medical)...72 6.3.8 CoreValve (Medtronic, Inc.)...73 6.3.9 Direct Flow valve (Direct Flow Medical)...76 6.3.10 Engager valve (Medtronic, Inc.)...79 6.3.11 Heart Leaflet Technology (Bracco SpA)...80 6.3.12 Innovare valve (Braile Biomedica)...81 6.3.13 JenaValve (JenaValve)...83 6.3.14 Portico valve (St. Jude Medical, Inc.)...84 Page 7 GDME1001CFR / Published NOV 2012
6.3.15 Sadra Lotus valve (Boston Scientific)...85 6.3.16 Sapien XT valve (Edwards Lifesciences)...87 6.3.17 Sapien 3 (Edwards Lifesciences)...89 6.3.18 Trinity valve (Transcatheter Technologies GmbH)...90 6.3.19 Vanguard Exchangeable Heart Valve System (ValveXchange)...91 6.4 Clinical Trial Analysis...94 6.4.1 Overview...94 6.4.2 Trials to Watch...94 6.4.3 Summary...96 7 Industry Overview...97 7.1 Procedure Trends...97 7.1.1 Reimbursement Hinders Adoption...97 7.2 Market Access...98 7.2.1 Adoption of TAVR...98 7.2.2 Heart Teams for Specialized Care...100 7.2.3 Facilities Enabling TAVR...102 7.2.4 Training and Protocols for Care...102 7.3 Reimbursement Trends... 103 7.4 Regulatory Issues/Recalls... 104 7.5 Mergers & Acquisitions/Key Partnerships...105 8 Current and Future Players... 107 8.1 Overview...107 8.2 Trends in Corporate Strategy...107 8.3 Company Profiles...108 8.3.1 AorTech International plc...108 8.3.2 Boston Scientific... 109 8.3.3 Bracco SpA...110 8.3.4 Braile Biomedica... 112 8.3.5 Colibri Heart Valve, LLC...113 Page 8 GDME1001CFR / Published NOV 2012
8.3.6 Direct Flow Medical... 114 8.3.7 Edwards Lifesciences, Inc...115 8.3.8 Hansen Medical... 117 8.3.9 JenaValve Technology... 118 8.3.10 Medtronic, Inc....119 8.3.11 Perouse Medical... 120 8.3.12 St. Jude Medical... 121 8.3.13 Symetis...123 8.3.14 Transcatheter Technologies GmbH...124 8.3.15 ValveXchange...125 9 Market Drivers, Opportunities and Barriers...127 9.1 Market Drivers...127 9.1.1 Superior to Conventional Treatment...127 9.1.2 New Alternative for Patients with No Options... 128 9.1.3 Expected Launch of CoreValve, Acurate TA, and Sapien XT in US...128 9.1.4 Expanded Approval in US...128 9.1.5 Supportive Imaging... 128 9.2 Opportunities...129 9.2.1 Repositionability... 130 9.2.2 Miniaturization of Valve Systems...130 9.2.3 Single Operator Devices...131 9.2.4 Lower Cost...131 9.2.5 Dilation Scoring Balloon...131 9.2.6 Removal of Native Valve Leaflets...132 9.2.7 Temporary Aortic Valves...132 9.3 Market Barriers...133 9.3.1 Reimbursement...133 9.3.2 Slow Adoption...133 9.3.3 Cost...133 Page 9 GDME1001CFR / Published NOV 2012
9.3.4 Substitutes...133 10 Country Outlooks & Forecasts... 135 10.1 US Markets Overview... 135 10.2 United States...137 10.2.1 United States Market Analysis...137 11 Appendix... 140 11.1 Abbreviations...140 11.2 Bibliography...142 11.3 Methodology...146 11.4 Coverage...146 11.5 Secondary Research... 147 11.6 Forecasting Methodology... 147 11.6.1 Diagnosed Aortic Valve Disease (AVD) Patients...148 11.6.2 Percent Transcatheter Aortic Valve Replacement Patients... 148 11.6.3 Pricing Assumptions... 148 11.6.4 Prevalence in Surgical Risk Segments... 148 11.6.5 Cost of Aortic Valve Disease...148 11.7 Physicians and Specialists Included in this Study...149 11.8 Primary Research...149 11.9 Physician Survey...150 11.10 About the Authors...151 11.10.1 Analysts...151 11.10.2 Global Head of Healthcare...152 11.11 Definitions...153 11.12 About GlobalData...154 11.13 Contact Us...154 11.14 Disclaimer...154 Page 10 GDME1001CFR / Published NOV 2012
1.1 List of Tables Table 1: Etiology of Single Left-Side Valve Disease...19 Table 2: Initial Presenting Symptoms of Aortic Valve Disease...22 Table 3: Basic Frequency of Examination...24 Table 4: Modifiers of Examination Frequency...24 Table 5: Cardiovascular Risk Factors and Comorbidities...25 Table 6: Investigations Performed to Diagnose AVD...26 Table 7: Basic Principles for Management of AVD Patients...27 Table 8: Aortic Valve Disease National Indirect and Direct Costs ($bn), 2009-2018...43 Table 9: TAVR Product Approvals by Date...45 Table 10: Assessment of TAVR Device Features...46 Table 11: Product Profile - Sapien...47 Table 12: Sapien SWOT Analysis, 2012...49 Table 13: TAVR Global Product Pipeline, 2012...63 Table 14: Product Profile - Acurate TA...64 Table 15: Acurate TA SWOT Analysis, 2012...65 Table 16: Product Profile - Acurate TF...66 Table 17: Acurate TF SWOT Analysis, 2012...67 Table 18: Product Profile - AorTech...67 Table 19: AorTech SWOT Analysis, 2012...68 Table 20: Product Profile - AorTx...69 Table 21: AorTx SWOT Analysis, 2012...70 Table 22: Product Profile - Centera...70 Table 23: Centera SWOT Analysis, 2012...71 Table 24: Product Profile - Colibri...71 Table 25: Colibri SWOT Analysis, 2012...72 Table 26: Product Profile - Cormove...73 Table 27: Cormove SWOT Analysis, 2012...73 Table 28: Product Profile - CoreValve...74 Page 11 GDME1001CFR / Published NOV 2012
Table 29: CoreValve SWOT Analysis, 2012...76 Table 30: Product Profile - Direct Flow...77 Table 31: Direct Flow SWOT Analysis, 2012...78 Table 32: Product Profile - Engager...79 Table 33: Engager SWOT Analysis, 2012...80 Table 34: Product Profile - Heart Leaflet Technology...80 Table 35: Heart Leaflet Technology SWOT Analysis, 2012...81 Table 36: Product Profile - Innovare...81 Table 37: Innovare SWOT Analysis, 2012...82 Table 38: Product Profile - JenaValve...83 Table 39: JenaValve SWOT Analysis, 2012...84 Table 40: Product Profile - Portico...84 Table 41: Portico SWOT Analysis, 2012...85 Table 42: Product Profile - Sadra Lotus...86 Table 43: Sadra Lotus SWOT Analysis, 2012...87 Table 44: Product Profile - Sapien XT...87 Table 45: Sapien XT SWOT Analysis, 2012...89 Table 46: Product Profile - Sapien 3...89 Table 47: Sapien 3 SWOT Analysis, 2012...90 Table 48: Product Profile - Trinity...91 Table 49: Trinity SWOT Analysis, 2012...91 Table 50: Product Profile - Vanguard...92 Table 51: Vanguard SWOT Analysis, 2012...93 Table 52: Company Profile - AorTech International plc... 108 Table 53: AorTech International SWOT Analysis, 2012... 109 Table 54: Company Profile - Boston Scientific...109 Table 55: Boston Scientific SWOT Analysis, 2012... 110 Table 56: Company Profile - Bracco SpA...111 Table 57: Bracco SpA SWOT Analysis, 2012...112 Page 12 GDME1001CFR / Published NOV 2012
Table 58: Company Profile - Braile Biomedica...112 Table 59: Braile Biomedica SWOT Analysis, 2012... 113 Table 60: Company Profile - Colibri Heart Valve...113 Table 61: Colibri Heart Valve SWOT Analysis...114 Table 62: Company Profile - Direct Flow Medical...115 Table 63: Direct Flow Medical SWOT Analysis, 2012... 115 Table 64: Company Profile - Edwards Lifesciences... 116 Table 65: Edwards Lifesciences SWOT Analysis, 2012... 117 Table 66: Company Profile - Hansen Medical...117 Table 67: Hansen Medical SWOT Analysis, 2012...118 Table 68: Company Profile - JenaValve Technology... 118 Table 69: JenaValve Technology SWOT Analysis, 2012... 119 Table 70: Company Profile - Medtronic...119 Table 71: Medtronic SWOT Analysis, 2012...120 Table 72: Company Profile - Perouse Medical...120 Table 73: Perouse Medical SWOT Analysis, 2012... 121 Table 74: Company Profile - St. Jude Medical...121 Table 75: St. Jude Medical SWOT Analysis, 2012... 122 Table 76: Company Profile - Symetis...123 Table 77: Symetis SWOT Analysis, 2012...123 Table 78: Company Profile - Transcatheter Technologies... 124 Table 79: Transcatheter Technologies SWOT Analysis, 2012...124 Table 80: Company Profile - ValveXchange...125 Table 81: ValveXchange SWOT Analysis, 2012...126 Table 82: Major Events Affecting the Global TAVR Market...136 Table 83: Sales Forecasts for TAVR in the US, 2011-2018...137 Table 84: Physicians Surveyed, By Country...150 Page 13 GDME1001CFR / Published NOV 2012
1.2 List of Figures Figure 1: Diagram of Human Heart...17 Figure 2: Strategy for Evaluating Heart Murmurs...23 Figure 3: General Treatment Modalities for Aortic Valve Disease...28 Figure 4: Aortic Valve Replacement Treatment Modalities in the US...29 Figure 5: Surgical Risk of Symptomatic, Severe AVD Patients, 2011...38 Figure 6: Prevalence of Moderate or Severe Valve Disease in US Population 2011...39 Figure 7: Prevalence of AVD in Patients 65+...39 Figure 8: Breakdown of Severe AVD Patients Receiving Surgical Valve Replacement & Transcatheter Valve Replacement...41 Figure 9: Total Costs at One Year for TAVR and SAVR as Calculated in 2011 in Europe...42 Figure 10:Companies in TAVR Market with Approved Devices...44 Figure 11:TAVR Device Attributes by Current Satisfaction and Importance, 2011...62 Figure 12:TAVR Pipeline by Stage in Clinical Development, 2012...63 Figure 13:TAVR Procedures Per Year...135 Figure 14:Sales Forecasts for TAVR in the US, 2011-2018...138 Page 14 GDME1001CFR / Published NOV 2012
Introduction 2 Introduction For patients suffering from severe aortic valve disease or valve dysfunction, percutaneous Transcatheter Aortic Valve Replacement (TAVR) enables implantation of a prosthetic heart valve within the diseased native aortic valve without the need for open heart surgery or cardiopulmonary bypass; TAVR provides a new therapeutic option for elderly patients who are considered to have high surgical risk or contraindications to open heart surgery, in addition to an alternative option for all other aortic valve disease patients. TAVR is becoming an increasingly popular alternative to open heart surgery as professional and commercial interest intensifies and effectiveness becomes proven; the percutaneous approach is less invasive and has a shorter recovery time compared with open-heart access. As approved indications for use of TAVR expand as well as more competitors enter the market, this industry will grow substantially in coming years. 2.1 Catalyst Transcatheter Aortic Valve Replacement offers a novel and groundbreaking technology for accessing the heart valves in patients who are extremely high-risk or inoperable candidates for conventional surgical valve replacement, with the expectation that this technology may be utilized in lower risk surgical candidates in the future. An estimated 55,000 patients worldwide have already undergone TAVR (Holmes et al., 2012). TAVR has been adopted in many centers in the US. As centers around the world improve their catheterization facilities as well as introduce training to their staff for TAVR procedures, it is expected that TAVR could be used on upwards of 10%-20% of the Aortic Valve Disease (AVD) population in coming years, and has an estimated 2018 market value of over $2 billion. This report examines procedural volumes in the US, as well as adoption trends for the quickly spreading TAVR procedure. With improvements in cardiac imaging and robotics, it s expected that TAVR procedures will be easier to perform in the future and have fewer associated side effects as training improves. Additionally, as TAVR is reliant on so many different types of technology, there is much room for improvement across the board in how these procedures are carried out. This report examines current unmet needs, opportunities for development and market penetration, expectations for an expanding target market, and associated complications with TAVR. This report looks at market breakdown by company, new entrants to the TAVR industry, and drivers for future growth. Page 15 GDME1001CFR / Published NOV 2012
Appendix 11.12 About GlobalData GlobalData is a leading global provider of business intelligence in the Healthcare industry. GlobalData provides its clients with up-to-date information and analysis on the latest developments in medical device research, disease analysis, and clinical research and development. Our integrated business intelligence solutions include a range of interactive online databases, analytical tools, reports and forecasts. Our analysis is supported by a 24/7 client support and analyst team. GlobalData has offices in New York, Boston, London, India and Singapore. 11.14 Disclaimer All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form by any means, electronic, mechanical, photocopying, recording or otherwise without the prior permission of the publisher, GlobalData. Page 154 GDME1001CFR / Published NOV 2012