Contents:

CHAPTER 1 3. Insight into the antidyslipidemics market 3 R&D pipeline dynamics 3 Guideline recommendations for an aggressive treatment approach emphasizes a need for more treatment options 4 Pfizer’s atorvastatin + torcetrapib combination to become a blockbuster drug 5 JTT-705- the most promising adjunct in development 6 CHAPTER 2 PIPELINE OVERVIEW & FUTURE FOCUS 17. Pipeline overview 17 PPAR agonists dominate the antidyslipidemic pipeline 20 Greatest number of drugs in Phase II of development 22 Pfizer has the greatest number of products in development 24 Heavy investment from Japanese-based pharmaceutical companies 26 Pfizer’s strategy to success 28 Pfizer protecting its revenue 28 Pfizer’s strategy under scrutiny 29 Thought needs to be given to pricing strategy 29 Merck – the loss of Zocor’s patent 31 Diversifying its portfolio 32 In-licensing 32 Expansion 33 Streamlining 34 HeartPro and Vytorin 34 CHAPTER 3 PIPELINE DYNAMICS 35. Definition of dyslipidemia 35 What is dyslipidemia? 35 Segmentation of dyslipidemia 36 Markers for dyslipidemia 36 Main types of dyslipidemia 36 Hypercholesterolemia 36 Familial hypercholesterolemia 37 Hypertriglyceridemia 38 Familial hypertriglyceridemia 38 Mixed dyslipidemia 38 Epidemiology of dyslipidemia 39 The greatest unmet need in dyslipidemia according to key opinion leaders, is for drugs with the ability to prevent or reverse atherosclerosis 44 Drugs need to prevent or even reverse the progression of atherosclerosis 45 Drugs with novel mechanisms of action 45 Drugs with increased efficacy in lowering LDL and increasing HDL 45 More long-term data is required to support primary and secondary prevention of acute CVD events. 46 More combination therapies are needed 46 Additional statin safety studies not required 46 CHAPTER 4 R&D APPROACH 48. Classification of pipeline products 48 Statins and statin combinations 51 Statins dominate the antidyslipidemic market 51 Mechanism of action 51 Atorvastatin + CETP inhibitor 52 Simvastatin + niacin 54 Fibrates – PPAR alpha agonists 57 Fibrate + biguanide 57 Other non-statin therapies 58 Acyl-CoA cholesterol acetyltransferase (ACAT) inhibitors 58 Ileal bile acid transport (IBAT) inhibitors 58 Lipoprotein lipase activator 59 Microsomal triglyceride transfer (MTP) inhibitors 59 Squalene synthetase inhibitor 59 Bile acid reabsorption inhibitor 59 Adenosine A1A receptor agonist 60 Apolipoprotein B100 antagonist 60 Dual PPAR agonists 60 PPAR delta agonist 61 VCAM inhibitor 61 Hypolipemic agent 61 Lipoprotein regulator 62 Transcription factor inhibitor 62 Cholesterol absorption inhibitors 62 Clinical trial design in dyslipidemia 62 Short term endpoints: controlling cholesterol levels 62 Long term endpoints: reduction in morbidity and mortality 63 CHAPTER 5 SINGLE-PILL STATIN COMBINATION LATE-STAGE DRUG ANALYSIS & FORECASTS 65. Overview for single-pill statin combination drugs 65 Pipeline summary 65 Definition of current comparator therapy 65 Pfizer’s Lipitor remains the current comparator therapy 66 Lipitor’s rise to prominence 66 KS-01-019 68 Clinical trials still underway 69 Good patient potential 69 Marketing of Advicor provides Kos with experience 70 KS-01-019 performance will depend on its long-term data 71 SWOT analysis 73 Forecast to 2015 73 Atorvastatin + torcetrapib 75 Extensive Phase III trial underway 75 Significant increases in HDL cholesterol seen in Phase II trials 76 Elevations of 16–91% in HDL are seen in Phase I trials 77 Good patient potential if it can prove to reduce the progression of CHD 77 Marketing strategy aims to help Pfizer retain monopoly 78 The overall performance of atorvastatin + torcetrapib combination is lower than atorvastatin 78 SWOT analysis 80 Forecast to 2015 81 Drug assessment summary 83 CHAPTER 6 FIBRATES AND FIBRATE COMBINATIONS LATE-STAGE DRUG ANALYSIS AND FORECASTS 86. Pipeline summary 86 Fenofibrate is the current comparator therapy 86 Fenofibrate + metformin single-pill combination 87 No clinical trial data 88 Limited patient potential 88 Previous experience in marketing fenofibrate and metformin should enable Merck and Fournier to market the drug successfully 88 Overall performance rated lower than fenofibrates 88 SWOT analysis 90 Forecast to 2015 90 LCP Feno 92 LCP Feno met both primary and secondary objectives in clinical trial 92 LCP Feno offers another choice of fibrate for physicians 92 Marketing partner for LCP Feno is unknown 93 LCP Feno’s performance rated lower than fenofibrate 93 SWOT analysis 95 Forecast to 2015 95 Drug assessment summary 97 CHAPTER 7 ADJUNCTIVE THERAPY LATE STAGE ANALYSIS 100. Pipeline summary 100 Three different comparator therapies 100 Implitapide 102 Phase II trials are ongoing 102 Phase I showed significant lowering of LDL of up to 58% 103 Potential alternative to statins 103 Co-marketing deal may boost sales 103 Implitapide’s performance rated lower than atorvastatin 104 Forecasts to 2015 105 JTT-705 106 34% increase in HDL in Phase II clinical trials 106 Excellent patient potential as adjunctive therapy 107 Marketing factors 107 JTT-705 shows better potential than Niaspan 107 Forecast to 2015 108 Pamaqueside 110 Phase I trial showed a 12% reduction in LDL cholesterol 110 Further trials required to determine patient potential 110 Pamaqueside will benefit from Pfizer’s marketing experience 110 Pamaqueside assessed performance lower than Zetia 111 Forecast to 2015 112 Gemcabene 113 Clinical trial data shows significant increases in HDL 113 Gemcabene needs to prove itself as an adjunct to perform well in the market 114 Gemcabene has Pfizer’s marketing strength behind it 114 The unavailability of long-term data lowers overall performance to poorer than fenofibrate 114 Forecasts to 2015 116 FM VP4 117 Phase I trials show excellent safety profile 117 Phase II trials still underway 118 Potential as a safe top-up drug 118 FM VP4 will require a marketing partner 119 Overall performance rated less than Zetia 119 Forecast to 2015 121 Drug assessment summary 122 CHAPTER 8 COMPARATIVE FORECASTS 125. CHAPTER 9 INNOVATIVE EARLY-STAGE PROJECTS 129. Gene therapy appears to be a key therapy in preclinical development for dyslipidemia 129 APPENDIX A 131 Epidemiology methodology 131 Forecast methodology 131 Methodology 131 US 131 Japan 132 France 133 Germany 133 Italy 134 Spain 134 UK 134 Drug assessment summary 134 Contributing experts 137 Bibliography 138 Epidemiology sources 138 US 138 Japan 138 France 138 Germany 138 Italy 138 Spain 139 UK 139 Clinical trial data 139 Report methodology 140