Cardiology Drug Licensing Opportunities, 2002 - Market Research Reports

Contents:

Cardiology Licensing Opportunities Analyses, Rating, and Ranking… A Worldwide Study

Table of Contents

Disclaimer .................................................................................................................................................................... i
Executive Summary .................................................................................................................................................... iii
I. Major Pharmacologic Classes and Their Roles in Treating Cardiovascular Disease............................................ 1
1. Making better use of available cardiovascular agents....................................................................................... 1
1.1 Angiotensin-converting enzyme (ACE) inhibitors.................................................................................... 1
1.2 Calcium channel blockers (CCBs) ............................................................................................................ 2
1.3 β-Blockers ................................................................................................................................................ 2
1.4 Digitalis .................................................................................................................................................... 3
1.5 Lipid-lowering agents ............................................................................................................................... 3
1.6 Thrombolytics .......................................................................................................................................... 3
1.7 Aspirin...................................................................................................................................................... 3
1.8 AICDs ...................................................................................................................................................... 4
1.9 PTCA ....................................................................................................................................................... 4
1.10 Stents........................................................................................................................................................ 4
II. Delphi Panel and Thought Leader Interview: Discussion and Summary of Cardiology Innovation .................. 5
1. Introduction...................................................................................................................................................... 5
1.1 Hypertension and atherosclerosis: primary drivers of morbidity and mortality ........................................ 5
1.2 Additional risk factors involved in the development of cardiovascular disease (CVD)............................ 5
1.3 Role of genomics in risk assessment and therapy ..................................................................................... 7
2. Results of the Delphi Panel interviews ............................................................................................................. 7
2.1 Hypertension ............................................................................................................................................ 7
2.1.1 Dual endopeptidase (Vasopeptidase) inhibitors................................................................................ 7
2.1.2 Endothelin antagonists..................................................................................................................... 8
2.1.3 Calcium channel blockers (CCBs).................................................................................................... 8
2.1.4 Angiotensin converting enzyme (ACE) versus angiotensin receptor blockers (ARBs).................... 9
2.1.5 Vascular stiffness (arteriosclerosis) ................................................................................................ 10
2.1.6 Mineralocorticoids – hypertension.................................................................................................. 10
2.1.7 Novel diuretics............................................................................................................................... 10
2.2 Atherosclerosis ....................................................................................................................................... 10
2.2.1 Inflammation as a target for atherosclerosis ................................................................................... 10
2.2.2 Nuclear hormone receptors ............................................................................................................. 11
2.2.3 Additional therapeutic approaches.................................................................................................. 12
2.3 Congestive heart failure (CHF) ............................................................................................................... 12
2.3.1 Remodeling and hypertrophy.......................................................................................................... 12
2.3.2 Mineralocorticoids – CHF .............................................................................................................. 13
2.4 Restenosis............................................................................................................................................... 13
2.5 Arrhythmia ............................................................................................................................................. 14
2.5.1 Need for safer agents ...................................................................................................................... 14
2.5.2 Impact of devices ............................................................................................................................ 14
2.6 Adenosine modulators............................................................................................................................ 14
2.7 Anticoagulants, antiplatelet and antithrombotics .................................................................................... 15
2.8 Role of endothelium in cardiovascular medicine .................................................................................... 17
2.9 Cell therapy: challenging the paradigm of regeneration.......................................................................... 17
2.10 Genomics................................................................................................................................................ 18
2.11 Delphi summary ..................................................................................................................................... 18
III. Acute Coronary Syndromes Business Development and Innovation Opportunities....................................... 21
1. Introduction to the disease state and its epidemiology.................................................................................... 21
2. Evaluation of innovation activities underway ................................................................................................. 21
3. Product technology analysis........................................................................................................................... 24
3.1 Assumption structure.............................................................................................................................. 26
3.1.1 Anticoagulants ............................................................................................................................... 27
3.1.2 Antiplatelet agents .......................................................................................................................... 28
3.1.3 Thrombolytics................................................................................................................................ 29
3.1.4 Cholesterol/ low-density lipoprotein (LDL)-reducing agents ......................................................... 29
3.1.5 Endothelin receptor antagonist ....................................................................................................... 29
3.1.6 Procedures...................................................................................................................................... 30
3.1.7 Other technologies .......................................................................................................................... 30
4. Market analysis and forecast.......................................................................................................................... 31
5. Business development and innovation opportunity identification................................................................... 33
IV. Angina Pectoris Business Development and Innovation Opportunities.......................................................... 45
1. Introduction to the disease state and its epidemiology.................................................................................... 45
2. Evaluation of innovation activities under way ................................................................................................ 45
3. Product technology analysis........................................................................................................................... 47
3.1 Assumption structure ...................................................................................................................... 26
3.1.1 Nitrates........................................................................................................................................... 49
3.1.2 Calcium Channel Antagonists......................................................................................................... 50
3.1.3 β-Blockers...................................................................................................................................... 50
3.1.4 Anticoagulants ............................................................................................................................... 50
3.1.5 ACE Inhibitors............................................................................................................................... 51
3.1.6 Gene therapy.................................................................................................................................. 51
3.1.7 Metabolic modulators ..................................................................................................................... 51
3.1.8 Procedures...................................................................................................................................... 52
3.1.9 Other technologies .......................................................................................................................... 52
4. Market Analysis and Forecast........................................................................................................................ 52
5. Business development and innovation opportunity identification................................................................... 55
V. Arrhythmia Business Development and Innovation Opportunities.................................................................... 61
1. Introduction to the disease state and its epidemiology.................................................................................... 61
2. Evaluation of innovation activities under way ................................................................................................ 62
3. Product technology analysis........................................................................................................................... 63
3.1 Assumption structure.............................................................................................................................. 66
3.1.1 Class I agents ................................................................................................................................. 66
3.1.2 Class II agents................................................................................................................................ 66
3.1.3 Class III agents............................................................................................................................... 67
3.1.4 Class III mixed agents..................................................................................................................... 67
3.1.5 Class IV agents ............................................................................................................................... 67
3.1.6 Adenosine agents ............................................................................................................................ 67
3.1.7 Digoxin .......................................................................................................................................... 67
3.1.8 Warfarin......................................................................................................................................... 68
3.1.9 Newer anticoagulants..................................................................................................................... 68
3.1.10 Other agents ................................................................................................................................... 68
3.1.11 Procedures/devices......................................................................................................................... 68
4. Market analysis and forecast.......................................................................................................................... 68
5. Business development and innovation opportunity identification................................................................... 70
VI. Atherosclerosis and Hyperlipidemia Business Development and Innovation Opportunities ......................... 75
1. Introduction to the disease state and its epidemiology.................................................................................... 75
2. Evaluation of innovation activities underway ................................................................................................. 76
3. Product technology analysis........................................................................................................................... 78
3.1 Assumption structure.............................................................................................................................. 81
3.1.1 Cholesterol/LDL-reducing agents................................................................................................... 81
3.1.2 Peroxisome proliferator-activated receptor (PPAR), RXR, LXR modulators ................................ 82
3.1.3 Anti-inflammatory agents ............................................................................................................... 83
3.1.4 Antiplatelet agents .......................................................................................................................... 84
3.1.5 Immunotherapy.............................................................................................................................. 84
3.1.6 Antibiotics...................................................................................................................................... 84
4. Market analysis and forecast.......................................................................................................................... 85
5. Business development and innovation opportunity identification................................................................... 88
VII. Congestive Heart Failure (CHF) Business Development and Innovation Opportunities ................................ 95
1. Introduction to the disease state and its epidemiology.................................................................................... 95
2. Evaluation of innovation activities underway ................................................................................................. 95
3. Product technology analysis......................................................................................................................... 100
3.1 Assumption structure............................................................................................................................ 103
3.1.1 ACE inhibitors .............................................................................................................................. 103
3.1.2 Angiotensin II receptor blockers (ARBs) ..................................................................................... 104
3.1.3 β-Blockers.................................................................................................................................... 104
3.1.4 Diuretics....................................................................................................................................... 105
3.1.5 Digoxin ........................................................................................................................................ 105
3.1.6 Inotropic agents............................................................................................................................ 105
3.1.7 Endothelin receptor antagonist ..................................................................................................... 105
3.1.8 Vasopeptidase inhibitors (VPIs) ................................................................................................... 106
3.1.9 Anti-inflammatory, immunotherapy ............................................................................................. 106
3.1.10 Gene therapy................................................................................................................................ 107
3.1.11 Other technologies ........................................................................................................................ 107
4. Market analysis and forecast........................................................................................................................ 107
5. Business development and innovation opportunity identification................................................................. 110
VIII. Hypertension Business Development and Innovation Opportunities............................................................ 117
1. Introduction to the disease state and its epidemiology.................................................................................. 117
2. Evaluation of innovation activities underway ............................................................................................... 118
3. Product technology analysis......................................................................................................................... 121
3.1 Assumption structure............................................................................................................................ 123
3.1.1 ACE inhibitors .............................................................................................................................. 124
3.1.2 Angiotensin II receptor blockers (ARBs) ..................................................................................... 125
3.1.3 α-Blockers.................................................................................................................................... 125
3.1.4 β-Blockers.................................................................................................................................... 126
3.1.5 CCBs (antagonists) ....................................................................................................................... 126
3.1.6 Diuretics....................................................................................................................................... 126
3.1.7 Vasopeptidase inhibitor ................................................................................................................ 127
3.1.8 Endothelin receptor antagonist ..................................................................................................... 127
3.1.9 Vasopressin antagonist (a diuretic) ............................................................................................... 128
3.1.10 Other technologies ........................................................................................................................ 128
4. Market analysis and forecast........................................................................................................................ 128
5. Business development and innovation opportunity identification................................................................. 131
IX. Angioplasty/Restenosis Business Development and Innovation Opportunities............................................ 139
1. Introduction to the disease state and its epidemiology.................................................................................. 139
2. Evaluation of innovation activities underway ............................................................................................... 140
3. Product technology analysis......................................................................................................................... 143
3.1 Assumption structure............................................................................................................................ 145
3.1.1 Heparin, heparinoids (anticoagulants) .......................................................................................... 145
3.1.2 GP IIb/IIIa inhibitors .................................................................................................................... 146
3.1.3 ADP receptor inhibitors ................................................................................................................ 146
3.1.4 Cell Adhesion Molecules (CAM) ................................................................................................. 146
3.1.5 Growth factor inhibitors................................................................................................................ 146
3.1.6 Molecular therapies...................................................................................................................... 147
3.1.7 Photosensitizers ............................................................................................................................ 147
3.1.8 Cell therapy.................................................................................................................................. 147
4. Market analysis and forecast........................................................................................................................ 147
5. Business development and innovation opportunity identification................................................................. 150
Appendix I Technology Platforms ............................................................................................................................ 155
Angiotensin converting enzyme (ACE) inhibitors................................................................................................ 155
Adenosine receptor agonists and antagonists........................................................................................................ 156
α-Blockers............................................................................................................................................................ 157
Aldosterone antagonists ....................................................................................................................................... 157
Angiotensin II (ANG II) receptor antagonists....................................................................................................... 158
Anticoagulants ..................................................................................................................................................... 159
Anti-infective agents ............................................................................................................................................ 163
Anti-inflammatory ............................................................................................................................................... 163
Antiplatelet agents................................................................................................................................................ 164
β-Blockers ............................................................................................................................................................ 166
Cholesterol-LDL reducing ................................................................................................................................... 166
Calcium channel blockers .................................................................................................................................... 167
Class I anti-arrhythmic agents.............................................................................................................................. 168
Class III anti-arrhythmic agents ............................................................................................................................ 169
Diuretics............................................................................................................................................................... 169
Endothelin (ET) antagonists................................................................................................................................. 169
HDL-increasing agents ........................................................................................................................................ 170
Inotropic agents.................................................................................................................................................... 171
Metabolic modulators .......................................................................................................................................... 172
Molecular therapies.............................................................................................................................................. 172
Na/H Exchange inhibitors .................................................................................................................................... 174
Nitrates................................................................................................................................................................. 174
Photosensitizers.................................................................................................................................................... 175
Peroxisome proliferator-activated receptor (PPAR) agonists ............................................................................... 176
Thrombolytics ...................................................................................................................................................... 176
Vasopeptidase inhibitors (VPIs) ........................................................................................................................... 177
Vasopressin antagonists ....................................................................................................................................... 178
Appendix II Company Profiles of Innovative Firms Representing Acquisitions, Licensing, and Co-marketing Opportunities in Cardiovascular Therapy ................................................................................................................. 181
Aderis................................................................................................................................................................... 181
Alteon................................................................................................................................................................... 181
Asahi Kasei (formerly Asahi Chemical) ............................................................................................................... 182
Avant Immunotherapeutics .................................................................................................................................. 182
Boehringer Ingelheim .......................................................................................................................................... 183
Corvas .................................................................................................................................................................. 184
Curis..................................................................................................................................................................... 184
CV Therapeutics (CVT)....................................................................................................................................... 185
Emisphere Technologies ...................................................................................................................................... 185
Esperion ............................................................................................................................................................... 185
Fujisawa ............................................................................................................................................................... 186
GLYCODesign .................................................................................................................................................... 186
ICOS .................................................................................................................................................................... 187
Idun ...................................................................................................................................................................... 187
Menarini............................................................................................................................................................... 188
Mochida ............................................................................................................................................................... 189
Mylan ................................................................................................................................................................... 189
NitroMed.............................................................................................................................................................. 190
Otsuka .................................................................................................................................................................. 190
bioMérieux-Pierre Fabre Group........................................................................................................................... 191
Sankyo Co. Ltd .................................................................................................................................................... 191
Schwarz Pharma................................................................................................................................................... 192
Sepracor ............................................................................................................................................................... 192
Trigen................................................................................................................................................................... 192
X-Ceptor Therapeutics......................................................................................................................................... 193
Yamanouchi ......................................................................................................................................................... 193

List of Figures

Figure ES-1 WW distribution of development by indication..................................................................................... vii
Figure ES-2 Product development activity in cardiovascular therapy by phase of development .............................viii
Figure ES-3 US phase of development .....................................................................................................................viii
Figure ES-4 Active development programs in each phase of development by disease indication ............................. ix
Figure ES-5 Active development programs in each phase of development by disease area....................................... ix
Figure ES-6 Unpartnered versus partnered programs by phase of development ......................................................... x
Figure ES-7 US market activity in 1999 by disease state .......................................................................................... xii
Figure ES-8 US market activity in 2001 by disease state .........................................................................................xiii
Figure ES-9 US market activity in 2012 by disease state .........................................................................................xiii
Figure 2.1 Interplay of major factors in cardiovascular disease, therapy and drug development ................................ 6
Figure 3.1 Market impact matrix for technology platforms in acute coronary syndrome treatment.......................... 26
Figure 3.2 WW forecast for acute coronary syndrome therapy by technology platform........................................... 27
Figure 4.1 Market impact matrix for technology platforms in stable angina and post-MI treatment......................... 49
Figure 4.2 WW forecast for stable angina and post-MI management by technology platform................................. 50
Figure 5.1 Market impact matrix for technology platforms in arrhythmia treatment................................................. 65
Figure 5.2 WW forecast for arrhythmia therapy by technology platform................................................................. 66
Figure 6.1 Market impact matrix for technology platforms in atherosclerosis/hyperlipidemia treatment ................. 80
Figure 6.2 WW forecast for atherosclerosis and hyperlipidemia management by technology platform.................... 82
Figure 7.1 Market impact matrix for technology platforms in congestive heart failure........................................... 102
Figure 7.2 WW forecast for congestive heart failure management by technology platform.................................... 104
Figure 8.1 Market impact matrix for technology platforms in hypertension therapy............................................... 123
Figure 8.2 WW forecast for hypertension therapy by technology platform............................................................. 125
Figure 9.1 Market impact matrix for technology platforms in restenosis treatment ................................................ 144
Figure 9.2 WW Forecast for angioplasty/restenosis management by technology platform..................................... 145
Cardiology Licensing Opportunities
Analyses, Rating, and Ranking… A Worldwide Study
List of Tables
Table ES-1 US market forecast for all cardiovascular therapy by therapeutic area .................................................... xi
Table ES-2 US market forecast for all cardiovascular therapy by technology........................................................... xv
Table ES-3 Opportunity sorting matrix for all cardiovascular therapies.................................................................xviii
Table 1.1 Major classes of pharmacologic agents and primary indications ................................................................. 2
Table 1.2 Added potential value of available cardiovascular pharmacologic agents and nonpharmacologic
intervention .......................................................................................................................................................... 3
Table 3.1 Acute coronary syndrome treatment. Active US development programs by technology platform and
clinical status...................................................................................................................................................... 25
Table 3.2 US market technology forecast – acute coronary syndrome ($millions).................................................... 32
Table 3.3 US market forecast for acute coronary syndrome by technology during selected time periods ($millions)
........................................................................................................................................................................... 33
Table 3.4 Acute coronary syndrome business development opportunities................................................................. 34
Table 3.5 Product development in acute coronary syndrome..................................................................................... 37
Table 4.1 Angina treatment. Active US development programs by technology platform and clinical status ............ 48
Table 4.2 US market technology forecast – angina and post-MI therapy ($millions)................................................ 54
Table 4.3 US market forecast for angina and post-MI therapy by technology during selected time periods
($millions).......................................................................................................................................................... 55
Table 4.4 Angina business development opportunities .............................................................................................. 56
Table 4.5 Product development in angina .................................................................................................................. 57
Table 5.1 Arrhythmia treatment. Active US development programs by technology platform and clinical status ..... 64
Table 5.2 US market technology forecast – arrhythmia ($millions) .......................................................................... 69
Table 5.3 US market forecast for arrhythmia therapy by technology during selected time periods ($millions) ........ 70
Table 5.4 Arrhythmia business development opportunities ....................................................................................... 71
Table 5.5 Product development in arrhythmia ........................................................................................................... 72
Table 6.1 Atherosclerosis treatment. Active US development programs by technology platform and clinical status 79
Table 6.2 US market technology forecast – atherosclerosis ($millions) .................................................................... 87
Table 6.3 US market forecast for atherosclerosis therapy by technology during selected time periods ($millions) .. 88
Table 6.4 Atherosclerosis business development opportunities ................................................................................. 89
Table 6.5 Product development in atherosclerosis ..................................................................................................... 91
Table 7.1 CHF treatment. Active US development programs by technology platform and clinical status .............. 101
Table 7.2 US market technology forecast – congestive heart failure ($millions)..................................................... 109
Table 7.3 US market forecast for congestive heart failure by technology during selected time periods ($millions)110
Table 7.4 Congestive heart failure business development opportunities.................................................................. 111
Table 7.5 Product development in congestive heart failure...................................................................................... 113
Table 8.1 Hypertension treatment. Active US development programs by technology platform and clinical status. 122
Table 8.2 US market forecast forecast for hypertension by technology ($millions) ................................................ 130
Table 8.3 US market forecast for hypertension by technology during selected time periods ($millions) ................ 131
Table 8.4 Hypertension business development opportunities .................................................................................. 132
Table 8.5 Product development in hypertension ...................................................................................................... 134
Table 9.1 Restenosis treatment. Active US development programs by technology platform and clinical status ..... 143
Table 9.2 US market forecast for restenosis therapy by technology ($millions)...................................................... 149
Table 9.3 US market forecast for restenosis by technology during selected time periods ($millions)..................... 150
Table 9.4 Restenosis business development opportunities....................................................................................... 151
Table 9.5 Product development in restenosis ........................................................................................................... 152