脂質代謝異常治療薬のパイプライン分析

INTRODUCTION

In the absence of pipeline compounds that can exceed the efficacy of statins, a number of trends have been identified. Pipeline developments are focusing on therapies that target lipid parameters inadequately controlled with statins, adjunctive therapies with novel mechanisms of action and statin/non-statin anti-dyslipidemic and statin/non anti-dyslipidemic single pill combinations

SCOPE OF THE REPORT

• Determination of the size of the hypercholesterolemia population in the seven major markets and summarization of the prevalence of low HDL cholesterol
• Quantitative overview of product development by class and phase to assess competitor activity and licensing opportunities
• In-depth analysis of clinical and market factors for late-stage statin and non-statin developmental therapies, including sales forecasts to 2011
• Overview of innovative early stage therapies, identifying promising development strategies and programs

REPORT HIGHLIGHTS

Although statins will continue to dominate the market, these drugs have been plagued by safety concerns, which have delayed the approval of both Crestor and Livalo.

The dyslipidemia R&D pipeline consists of 15 novel classes and increased availability of adjunctive therapies will lead to vast improvements in the treatment of more 'difficult-to-treat' patients.

Following greater acceptance of combination therapy, current developments are focusing on multi-modal therapies and statin single pill combinations.

KEY REASONS OT BUY THIS REPORT

• Recognize key areas within the current treatment of dyslipidemia that are inadequately served
• Gain an independent view of the R&D activity in the market
• Determine the gaps in the market, in order to position developmental products, and identify lucrative licensing and co-marketing opportunities

TABLE OF CONTENTS

CHAPTER 1 EXECUTIVE SUMMARY 3

• Scope of the analysis 3
• Datamonitor insight into the dyslipidemia market 4
• Summary 10
• Key metrics 12

CHAPTER 2 PATIENT POTENTIAL 25

• Definition of dyslipidemia 26
• What is dyslipidemia? 26
• Segmentation of dyslipidemia 26
• Markers for dyslipidemia 26
• Which markers are the best indicators of cardiovascular risk? 27
• Main types of dyslipidemia 30
• Hypercholesterolemia 30
• Familial hypercholesterolemia 31
• Hypertriglyceridemia 31
• Familial hypertriglyceridemia 32
• Mixed dyslipidemia 32
• Epidemiology of dyslipidemia 32
• Prevalence of hypercholesterolemia 32
• Methodology 35
• Little change in cholesterol among US adults in 1999-2000 39
• Prevalence of low HDL cholesterol 39
• Unmet need in dyslipidemia 41
• Disease management unmet needs 41
• More comprehensive screening and diagnosis of patients 42
• More eligible patients receiving therapy 42
• Improved titration of statin doses 43
• Improved compliance and patient education 43
• More cost-effective care 45
• Clinical unmet needs: Opinion leader views 46
• Increased efficacy in HDL raising 47
• Combination therapies to treat patients with complicated lipid profiles (including adjuncts and single pill combinations) 48
• Drugs with differing mechanisms of action 49
• Ability to prevent or even reverse the progression of atherosclerosis 49
• Increased efficacy in LDL cholesterol lowering 50
• Long term data to support primary/secondary prevention of acute CVD events 51
• Further statin safety studies 51

CHAPTER 3 R&D APPROACH 52

• Characteristics of the current anti-dyslipidemic market 53
• The current comparator therapy: Pfizer' s Lipitor 54
• Lipitor' s rise to prominence 54
• The accumulation of clinical trial support 54
• Classification of pipeline products 57
• Statins 59
• Dominating the anti-dyslipidemic market 59
• Mechanism of action 59
• The development of statin single pill combinations 60
• Non-statin anti-atherosclerotic therapies 62
• ACAT inhibitors: a problematic past 62
• CETP inhibitors: targeting HDL cholesterol 63
• MTP inhibitors: failure of many compounds 63
• IBAT inhibitors: still too early to tell? 64
• Other novel non-statin therapies 65
• Dual PPAR agonists: improving insulin sensitivity and lipid profiles 65
• Bile acid sequestrants: use limited by side-effects 66
• Squalene synthase inhibitors: inhibiting the cholesterol production pathway 66
• The future: the introduction of the 'Polypill'  67
• Clinical trial design in dyslipidemia 69
• Clinical trial design criteria: Opinion leader views 70
• Use of hard versus soft endpoints 71
• Number of patients enrolled and length of study 72
• Use of a variety of lipid markers 73
• Use of the gold standard as the comparator drug 74
• Clinical trial endpoints in dyslipidemia 75
• Phase I trials: establishing safety and tolerability 76
• Phase II and beyond: establishing efficacy 76
• Short term endpoints: controlling cholesterol levels 76
• Long term endpoints: reduction in morbidity and mortality 77

CHAPTER 4 DYSLIPIDEMIA PIPELINE ANALYSIS 79

• Pipeline overview 80
• Key companies involved in the dyslipidemia pipeline 83
• Multinational companies involved in anti-dyslipidemic R&D 84
• Pfizer: R&D strategies to maintain success 84
• Merck & Co.: defensive strategies 88
• The presence of Japanese companies in the dyslipidemia market 92
• Companies with anti-dyslipidemic sales and marketing experience 93
• Companies without anti-dyslipidemic sales and marketing experience 95
• Licensing opportunities with specialty US-based companies 96

CHAPTER 5 STATIN AND STATIN COMBINATION DRUG ANALYSIS & FORECASTS 97

• Overview for the statin class 98
• Pipeline summary 98
• Livalo (pitavastatin) 99
• Profile 99
• Drug overview 99
• Clinical trial data 100
• Patient potential 105
• Marketing factors 106
• Performance indicators 107
• SWOT analysis 110
• Forecasts to 2011 111
• Caduet (Lipitor + Norvasc single pill) 113
• Profile 113
• Drug overview 113
• Clinical trial data 113
• Patient potential 116
• Marketing factors 119
• Performance indicators 120
• SWOT analysis 122
• Forecasts to 2011 122
• Zocor (simvastatin) + Zetia (ezetimibe) single pill 124
• Profile 124
• Drug overview 124
• Clinical trial data 126
• Patient potential 139
• Marketing factors 145
• Performance indicators 146
• SWOT analysis 150
• Forecasts to 2011 150

CHAPTER 6 NON-STATIN ANTI-ATHEROSCLEROTIC DRUG ANALYSIS AND FORECASTS 153

• Overview for the non-statin anti-atherosclerotic class 154
• Pipeline summary 154
• Definition of current comparator therapy 155
• AGI-1067 155
• Profile 155
• Drug overview 155
• Clinical trial data 156
• Patient potential 159
• Marketing factors 159
• Performance indicators 160
• SWOT analysis 163
• Forecasts to 2011 163
• CETi-1 165
• Profile 165
• Drug overview 165
• Clinical trial data 165
• Patient potential 167
• Marketing factors 168
• Performance indicators 169
• SWOT analysis 171
• Implitapide (BAY-13-9952) 172
• Drug overview 172
• Clinical trial data 172
• Patient potential 174
• Marketing factors 174
• Performance indicators 175
• SWOT analysis 178
• Other non-statin anti-atherosclerotic agents 178
• CETP inhibitors 178
• Torcetrapib (CP-529,414) 178
• JTT-705 186
• ACAT inhibitors 188
• Eflucimibe 188
• CS-505 188
• IBAT inhibitors 189
• S-8921 189
• BARI-1453 189
• Lp-PLA2 inhibitors 190
• SB480848 and 659032 190
• Others 191
• NO-1886 191
• Gemcabene (CI-1027) 191
• AC3056 192
• Projects on hold 192
• Avasimibe (C-1011) 192
• Drug overview 192
• Clinical trial data 193

CHAPTER 7 'OTHER'  NOVEL NON-STATIN DRUG ANALYSIS 195

• Overview for the 'other'  novel non-statin class 196
• Pipeline summary 196
• Definition of current comparator therapy 197
• FM-VP4 197
• Profile 197
• Drug overview 197
• Clinical trial data 197
• Patient potential 199
• Marketing factors 200
• SWOT analysis 201
• Additional agents in the 'other'  novel non-statin class 201
• Dual PPAR agonists 201
• KRP-297 201
• Galida (tesaglitazar/AZ242) 202
• Muraglitazar (BMS-298585) 202
• Compounds in development with GlaxoSmithKline and Eli Lilly 203
• Bile acid sequestrants 203
• GT102-279 203
• Squalene synthase inhibitors 203
• TAK-475 203
• Others 204
• PLT 732 204

CHAPTER 8 COMPARATIVE ANALYSIS 205

• Comparison of key anti-dyslipidemic compounds 205
• Comparison of performance indicators 205
• Efficacy 206
• Side-effects 206
• Availability of long term data 206
• Direct effect on atherosclerosis 206
• Patient potential 207
• Marketing strength 207
• Overall performance 207
• Comparative forecasts 208

CHAPTER 9 INNOVATIVE EARLY-STAGE PROJECTS 210

• Most promising early stage innovative therapies 210
• Esperion: targeting the RLT pathway 210
• ESP 31015: Esperion' s most advanced small molecule 211
• Gene therapy for dyslipidemia 211
• Genetic targets in dyslipidemia 211
• Limited potential for gene therapy in treating dyslipidemia? 213
• Key research impacts on the dyslipidemia market 214

CHAPTER 10 INTERVIEW TRANSCRIPTS 216

• Dr Anthony Wierzbicki, UK 216
• Diagnosis and patient types 217
• Unmet needs in dyslipidemia 219
• Treatment outcomes 220
• Research and clinical trial impacts 222
• Third generation statins 228
• Use of adjunctive therapy (such as niacin, colesevelam and ezetimibe) 230
• Single pill combination therapies 232
• Innovative therapy 234
• Dr Michael Davidson, US 234
• Diagnosis and patient types 235
• Unmet needs in dyslipidemia 237
• Treatment outcomes 238
• Research and clinical trial impacts 239
• Third generation statins 243
• Use of adjunctive therapy (such as niacin, colesevelam and ezetimibe) 244
• Single pill combination therapies 246
• Innovative therapy 248
• Dr Robert Knopp, US 248
• Diagnosis and patient types 249
• Unmet needs in dyslipidemia 251
• Treatment outcomes 252
• Research and clinical trial impacts 254
• Third generation statins 258
• Use of adjunctive therapy (such as niacin, colesevelam and ezetimibe) 259
• Single pill combination therapies 260
• Professor John Chapman, France 261
• Diagnosis and patient types 262
• Unmet needs in dyslipidemia 264
• Treatment outcomes 265
• Research and clinical trial impacts 267
• Third generation statins 273
• Use of adjunctive therapy (such as niacin, colesevelam and ezetimibe) 274
• Single pill combination therapies 276
• APPENDIX A 278
• List of tables 278
• List of figures 281
• Bibliography 283
• Epidemiology sources 283
• US 283
• Japan 283
• France 283
• Germany 283
• Italy 283
• Spain 284
• UK 284
• Clinical trial data 284

APPENDIX B 288

• About Datamonitor 288
• About Datamonitor Healthcare 288
• Datamonitor Healthcare' s research and analysis methodologies 289
• Datamonitor Healthcare' s therapy area capabilities 289
• About Disease analysis team 290