Pipeline Insight: Dyslipidemia - Shift from statins to add-ons

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