Strategic Perspectives: Antidyslipidemics Current market is not conducive for growth

About the cardiovascular pharmaceutical analysis team 2

CHAPTER 1 EXECUTIVE SUMMARY 3
Strategic scoping and focus 3
Datamonitor insight into the disease market 3
Related reports 5
Upcoming related reports 5

CHAPTER 2 MARKET DEFINITION 7
Market definition for this report 7

CHAPTER 3 MARKET OVERVIEW 8
US 8
Current market assessment 8
Future market assessment 11
Opportunities 12
Price of drugs 12
Leveraging the NCEP ATP III guidelines 13
Direct-to-consumer (DTC) advertising is legal in the US and has been shown to influence patient prescription choice and increase diagnosis rates 13
Threats 14
High-profile generic entrants into the statin class could slow growth 14
Medicare and Medicaid 15
Drug importation 16
Pricing and reimbursement issues 16
Curbing of DTC advertising will lead to greater emphasis on risk of products 17
Wal-Mart $4 a day generic program introduces further cost competition 18
The FDA's increasing safety focus 19
Changes in the US patent law may weaken the position of Pharma 20
Japan 22
Current market assessment 22
Future market assessment 24
Opportunities 25
Aging population 25
An underdeveloped generics market slows brand erosion 26
Multiple Patent Extensions and Labeling Regulations 26
Harmonization of approval process and opening up the Japanese market 27
Drug approval lag-time being targeted by the Japanese Ministry of Health, Labour and Welfare 28
Reduced product approval time 29
The Internet is an effective means to reach out to patients 29
Threats 30
Despite being underdeveloped, generics are expected to evolve into a significant player in the Japanese healthcare market in the future 30
Biennial price cuts still threaten market growth 32
Complex regulatory process 32
New healthcare reforms under debate 33
Flat-sum reimbursement discourages physicians from prescribing highly priced medicines 34
France 35
Current market assessment 35
Future market assessment 38
Opportunities 38
Innovation encouraged in the pharmaceutical industry 38
Consumers in France readily recognize the Internet as a source of high-quality medical information 39
Generic consumption in France is particularly low 39
Threats 39
Continuation of cost-control measures 39
Reference price system 40
Formulary access 41
Take-off of generic sector 41
Pharmacists are being mandated to drive generic dispensing 43
Germany 45
Current market assessment 45
Future market assessment 48
Opportunities 48
Pricing freedom which supports innovation 48
Reimbursement is granted to almost all drugs 49
ePharmacy and mail-order drugs legalized 49
Threats 50
Cost-containment measures in Germany have led to a healthy generics market 50
German doctors set to receive bonuses for prescribing generics 52
Italy 53
Current market assessment 53
Future market assessment 56
Opportunities 56
Single agency holds regulatory authority 56
Negligible impact of generics 57
Innovative drug development rewarded with premium price and 100% reimbursement 58
Threats 58
Ongoing cost-containment measures 58
Restructured reimbursement categories 60
Intellectual property to conform with rest of EU 61
Spain 62
Current market assessment 62
Future market assessment 66
Opportunities 66
New initiatives to improve prevention 66
Traditionally underdeveloped generics market 67
Threats 67
Complex pricing system 67
Increased scrutiny of new drugs 68
Compulsory patient co-payments 68
Government awareness campaign promotes generic use 68
UK 70
Current market assessment 70
Future market assessment 74
Opportunities 74
Attractiveness of market 74
Supplementary and expanded prescribing powers 75
Taking the GMS contract to the next level 75
Fast-track drug assessment process speeds up time between licensing and NICE recommendations 77
Threats 77
The National Institute for Health and Clinical Excellence (NICE) 77
2009 PPRS is expected to be more stringent than 2005 PPRS 79
Cost-containment measures encourage continued high use of generics 80
Rest of World snapshot 80
Current market assessment 81

CHAPTER 4 BRAND DYNAMICS 83
Overview of competitive landscape 83
Drivers of prescription choice 86
Cost becoming more important than efficacy and safety: generics 86
Cost playing a role in the brand choice: formulary status 89
Lipitor - the would-be gold standard 90
Drug profile 90
Product positioning 92
Brand forecast to 2017 93
Strategic recommendations 95
Vytorin - the success of an SPC 97
Drug profile 97
Product positioning 98
Vytorin's sales plateau 99
Brand forecast to 2017 99
Strategic recommendations 102
Crestor - the newest statin is on the rise 103
Drug profile 103
Product positioning 104
Brand forecast to 2017 105
Strategic recommendations 108
Pipeline - making it to the top 10? 109
TriLipix - joining the list 113
Development overview 113
Product positioning 114
Drug forecast to 2017 115
The rest of the pipeline - the reasons behind the lack of blockbuster 116
Livalo - not fitting into the overcrowded market 116
Dalcetrapib and anacetrapib - CETP inhibitors still under scrutiny 117
Mipomersen - the niche success? 120
Fenoglide - what does the new fenofibrate have to offer? 122
Cordaptive - more tolerable, but is it worth the risks? 123
Statin SPCs - waging the battle with generics unarmed? 126

CHAPTER 5 KEY PLAYERS 127
Strategic overview 127
Trends in corporate strategy 130
Pfizer 130
Corporate strategy 130
Antidyslipidemic portfolio assessment 131
Merck & Co. 132
Corporate strategy 132
Antidyslipidemic portfolio assessment 132
AstraZeneca 133
Corporate strategy 133
Antidyslipidemic portfolio assessment 133
Abbott 134
Corporate strategy 134
Antidyslipidemic portfolio assessment 134

CHAPTER 6 CASE STUDIES AND FORECAST SCENARIOS 136
TriLipix - will fenofibrate stay evergreen? 136
TriLipix - will Abbott's fenofibrate continue the domination? 139
Surrogate end points in dyslipidemia - a matter of the past? 140
ILLUMINATE puts HDL cholesterol into the spotlight 140
Torcetrapib's fiasco 140
The future of anacetrapib and dalcetrapib still in the dark 141
ENHANCE undermines trust in LDL cholesterol 142
Vytorin - is lower still better? 146
Potential impact of ENHANCE 147
Surrogate end points in dyslipidemia - an out of date concept? 149
Impact of ILLUMINATE and ENHANCE on drug development 149
SPCs - conquering the new horizons? 151
The first SPC - Vytorin 151
SPCs - aggressive marketing and significant advantages required 153
Development of the SPCs in the future 153
IMPROVE-IT - waiting for the new perspective on Zetia and Vytorin 157
Overview and importance of the study 157
IMPROVE-IT - worst and best case scenarios 158
Worst case scenario 158
Best case scenario 159
CETP Inhibitors 162
CETP inhibitors: the past and the future; what will be needed for successful launch? 162
Overview of the mechanism of action 162
HDL raising is one of the most important unmet needs 163
Torcetrapib - the most promising agent in development in 2006 165
CETP inhibition in general 173
Hypertension as a side effect of torcetrapib 173
Failure of torcetrapib - potential reasons 175
Anacetrapib and dalcetrapib - same mechanism of action, same outcome? 177
CETP inhibitors - what can be done to ensure successful launch? 180
CETP Inhibitors - worst and best case scenarios 181
Cordaptive and the FDA 185
Cordaptive/Tredaptive: the improved niacin not good enough for the FDA 185
Reasons for the non-approval and what it says about the FDA 186
Potential consequences may make Europe a more attractive market for launch 188
THRIVE: the light at the end of the tunnel? 189
UK: NICE recent guidelines - a nice surprise? 190
NICE Lipid Modification Guidelines - the driver of market expansion 190
NICE-led expansion of the market - an opportunity for Pharma? 191
BIBLIOGRAPHY 193
Journal papers 193
Websites 197
Datamonitor reports 205

APPENDIX A - MARKET ASSUMPTIONS 207
New product launches 207
Patent expiries 208
Data definitions, limitations and assumptions 209
Standard units 209
Japanese market data 209
Derivation of sales forecasts and pricing trends 209
Forecast methodology 209

APPENDIX B 211
Contributing experts 211
Experts contributing to this report 211
Experts contributing to previous reports 211
Report methodology 211
About Datamonitor 212
About Datamonitor Healthcare 212
About the cardiovascular analysis team 213
Disclaimer 214

List of Tables
Table 1: US sales and growth of drug classes in the antidyslipidemic market, 2007 9
Table 2: Japan sales and growth of drug classes in the antidyslipidemic market, 2007 22
Table 3: An example of the savings to be realized by using generic drugs in Japan, 2006 31
Table 4: France sales and growth of drug classes in the antidyslipidemic market, 2007 35
Table 5: Germany sales and growth of drug classes in the antidyslipidemic market, 2007 45
Table 6: Italy sales and growth of drug classes in the antidyslipidemic market, 2007 53
Table 7: Spain sales and growth of drug classes in the antidyslipidemic market, 2007 63
Table 8: UK sales and growth of drug classes in the antidyslipidemic market, 2007 71
Table 9: The 10 clinical areas of the Quality Outcome Framework, as outlined in the GMS contract, 2005 76
Table 10: Formulary status in the US for leading brands in dyslipidemia, 2007 89
Table 11: Lipitor: key facts, 2008 91
Table 12: Sales forecast ($m) for Lipitor in the seven major markets ($m), 2007-2017 93
Table 13: Impacting factors on Lipitor revenues, 2008-2017 95
Table 14: Vytorin: key facts, 2008 98
Table 15: Sales forecast for Vytorin in the seven major markets ($m), 2008-2017 100
Table 16: Impacting factors on Vytorin, revenues, 2007-2017 102
Table 17: Crestor: key facts, 2008 104
Table 18: Sales forecast for Crestor in the seven major markets ($m), 2007-2017 105
Table 19: Impacting factors on Crestor revenues, 2008-2017 108
Table 20: Summary of pipeline antidyslipidemic agents that are likely to launch with the forecast period, 2008-2017 111
Table 21: Sales forecast ($m) for TriLipix for dyslipidemia in the 7MM, 2007-2017 115
Table 22: Impacting factors on the revenues of TriLipix, 2007-2017 115
Table 23: Leading 10 companies in the seven major markets dyslipidemia market, 2007-2017 128
Table 24: Strategic importance of antidyslipidemic drugs to leading companies' portfolios, 2007 129
Table 25: Summary of statin-containing SPCs that are likely to launch within the forecast period, 2007-2017 154
Table 26: Phase II trial results for the atorvastatin + torcetrapib combination 167
Table 27: Mean percentage increase in HDL-C 168
Table 28: Mean percentage decrease in LDL-C 168
Table 29: Patient discontinuation results 169
Table 30: Summary of torcetrapib's late-stage clinical development, 2006 170
Table 31: Datamonitor's launch dates for antidyslipidemics in the 5EU and US, 2008-2017 207
Table 32: Patent expiry dates for the approved antidyslipidemics in the seven major markets, 2008-2017 208

List of Figures
Figure 1: Annual US sales ($m)of the antidyslipidemic drug classes, 2004-07 10
Figure 2: Performance of the key antidyslipidemic therapies in the US ($m), 2006-07 11
Figure 3: Market share of antidyslipidemic drugs in the US, 2007 versus 2017 12
Figure 4: New US Patent and Trademark Office (PTO) rules are unfavorable for Pharma and biotech 21
Figure 5: Annual Japan sales of the antidyslipidemic drug classes, 2004-07 23
Figure 6: Performance of the key antidyslipidemic therapies in Japan ($m), 2006-07 24
Figure 7: Market share of antidyslipidemic drugs in Japan, 2007 versus 2017 25
Figure 8: Annual France sales of the antidyslipidemic drug classes, 2004-07 36