Osteoporosis Intermittent dosing drives market growth

ABOUT DATAMONITOR HEALTHCARE 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the osteoporosis market 4
Key metrics 5
Datamonitor Pipeline Assessment Summary 6
CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS 21
Pipeline overview 23
Traditional, well-stocked pipeline 23
Growing PTH class hints at upcoming innovation 24
Reformulation as a substitute for innovation 25
Osteoporosis drug development not limited to big pharma 25
Key companies involved in the osteoporosis pipeline 25
Merck & Co.: coping with change 25
Merck's line expands, but the patent is wide open 26
Limited hope in the pipeline 27
Novartis: an old player with new strategies 27
Osteoporosis indication a key driver in Zometa growth 27
New classes and patent expiration represent threats 28
GlaxoSmithKline: A newcomer with a long-term approach 30
Boniva as a learning curve 30
Pipeline hints at future success 30
Key R&D company strategies 30
Optimizing administration 31
Yearly dosing has potential as the next stage in intermittent dosing 31
Options in delivery mode maintain whole brand sales 32
The addition of mineral supplements: calcium and vitamin D 32
Additional dose calcium satisfies physicians' demands 33
Combining vitamin D aids Merck's key brand's lifecycle 34
Genericization: if you can not beat them, join them 34
CHAPTER 3 OSTEOPOROSIS - MARKET POTENTIAL 36
Definition of osteoporosis 36
Etiology of osteoporosis 37
Osteoporosis classification: primary and secondary 37
Pathology and complications 38
Development of osteoporosis drugs 39
Segmentation of osteoporosis 40
Severity 40
Gender: osteoporosis in men 42
Niche populations 42
Glucocorticoid-induced osteoporosis 43
Paget's disease 44
CNS disorder-related fracture risk 45
Ethnic diversity 46
Prostate cancer 46
Premature menopause 47
HIV 48
Anorexia nervosa 48
Epidemiology of osteoporosis 49
Methodological difficulties in assessing prevalence 49
Prevalence of osteoporosis and osteopenia in postmenopausal women 50
Overview of the prevalence of osteoporosis and osteopenia in postmenopausal women 51
US 54
Japan 54
France 55
Germany 56
Italy 56
Spain 57
UK 58
Prevalence of osteoporosis and osteopenia in men 58
Introduction 58
Overview of the prevalence of osteoporosis/osteopenia in men 59
US 60
Japan 61
France 61
Germany 62
Italy 62
Spain 62
UK 63
Osteoporotic fractures, their implications and minor risk groups 63
Introduction 63
Limitations of fracture prevalence data 64
Overview of fracture prevalence 64
US 65
Japan 66
France 66
Germany 67
Italy 67
Spain 67
UK 68
Epidemiological trends 69
Unmet needs in osteoporosis 71
Unmet clinical needs 71
Need for improved compliance 71
Need for efficacy at least equivalent to Fosamax and Actonel 73
Need for surrogate endpoint efficacy 74
Need for efficacy at the hip 75
Unmet environmental needs 75
Need for increased patient identification, treatment rates and use of appropriate treatments in each patient 76
Need for primary prevention in osteoporosis - preventing the first fracture reduces the future fracture burden 77
Need for greater recognition of secondary causes of osteoporosis 79
Need for greater recognition of male osteoporosis and causes of secondary osteoporosis in men for screening or case-finding purposes 80
CHAPTER 4 R&D APPROACH 81
Classification of pipeline products 81
Bisphosphonates 81
Mechanism of action 82
Class breakdown 83
The gold standard therapy: Fosamax 83
Bisphosphonates threatened by genericization 84
Pipeline bisphosphonates 86
SERMs 86
Mechanism of action 86
Pipeline SERMs 87
Calcitonins 87
Mechanism of action 88
Pipeline calcitonins 89
Parathyroid hormone (PTH) and analogues 89
Mechanism of action 90
Pipeline PTH 90
Dual action bone agents (strontium ranelate) 91
Mechanism of action 91
Pipeline DABAs 92
Hormone replacement therapy (HRT) 92
Mechanism of action 92
Class breakdown 92
Pipeline hormonal therapies 93
Vitamin D 93
Mechanism of action 94
Pipeline vitamin D 95
Other mechanisms of action 95
Monoclonal antibodies 96
Cathepsin K inhibitors 96
Clinical trial design in osteoporosis 97
Clinical trial guidelines 97
Pre-clinical planning: use of animal models 97
Prevention and treatment: the implications for endpoint selection 98
Trial design and study population 99
Osteoporosis trial design and execution: can anything replace fracture data? 99
Problems with definitions: a need for greater consistency 99
Large-scale trials: can surrogate endpoints ever predict fracture risk? 99
The ethics of placebo-controlled trials: is there a realistic alternative? 100
Recruiting the right study population 101
Clinical trial endpoints in osteoporosis 101
Fracture rate 102
Significance of fracture rate as an endpoint 102
Considerations with fracture endpoints 103
Changes in BMD 104
Significance of BMD as an endpoint 104
Limitations of BMD as a clinical trial endpoint 105
Biochemical markers of bone turnover 106
How useful are bone markers? 107
Limitations in the use of bone-specific markers 107
Surrogate endpoints: predicting fracture risk 108
Changes in bone microarchitecture 108
Problems associated with microarchitecture assessment 109
CHAPTER 5 BISPHOSPHONATE LATE-STAGE DRUG ANALYSIS AND FORECASTS 110
Comparative forecasts 110
Comparative Datamonitor drug assessment summaries 111
Overview for bisphosphonates 111
Definition of current comparator therapy - Fosamax 112
Clinical trial data 113
Aclasta/Reclast (zoledronate/zoledronic acid) 115
Drug profile 115
Clinical trial data 115
Patient potential 117
Marketing factors 121
Satisfaction of unmet needs 122
Forecasts to 2016 123
Datamonitor drug assessment summary 126
Bisponal/ONO-5920 (minodronic acid hydrate) 126
Drug profile 126
Clinical trial data 127
Patient potential 129
Market potential 130
Satisfaction of unmet needs 130
Forecasts to 2016 131
Datamonitor drug assessment summary 133
MER-103 (alendronate sodium) 133
Drug profile 133
Clinical trial data 134
Patient potential 135
Market potential 136
Satisfaction of unmet needs 136
Forecasts to 2016 137
Datamonitor drug assessment summary 139
Other drugs in the bisphosphonate class 139
Nerixia (neridronic acid) 139
Abiogen's expertise may offset a halting development 139
CHAPTER 6 SERMS LATE-STAGE DRUG ANALYSIS AND FORECASTS 141
Overview for SERMs 141
Definition of current comparator therapy - Evista 142
Bazedoxifene 144
Drug profile 144
Clinical trial data for the treatment of osteoporosis 145
Clinical trial data for the prevention of osteoporosis 145
Patient potential 147
Marketing factors 148
Satisfaction of unmet needs 150
Forecasts to 2016 151
Datamonitor drug assessment summary 153
Other drugs in the SERM class 153
Arzoxifene (LY353381) 153
Lilly's Evista follow on? 153
PSK-3471 155
CHAPTER 7 CALCITONIN LATE-STAGE DRUG ANALYSIS AND FORECASTS 156
Overview for calcitonins 156
Definition of current comparator therapy - Miacalcin 156
Clinical trial data 157
BN-002 158
Drug profile 158
Clinical trial data 159
Patient potential 160
Marketing factors 161
Satisfaction of unmet needs 162
Forecasts to 2016 162
Datamonitor drug assessment summary 164
CHAPTER 8 PTH LATE-STAGE DRUG ANALYSIS AND FORECASTS 166
Comparative forecasts 166
Comparative Datamonitor drug assessment summaries 166
Overview of PTH 167
Definition of current comparator therapy - Forteo 168
hPTH (1-34) 170
Drug profile 170
Clinical trial data 170
Patient potential 171
Marketing factors 172
Satisfaction of unmet needs 172
Forecasts to 2016 173
Datamonitor drug assessment summary 175
Ostabolin-C 175
Drug profile 175
Clinical trials 176
Patient potential 177
Marketing potential 177
Satisfaction of unmet need 178
Forecasts to 2016 178
Datamonitor drug assessment summary 180
Other drugs in the PTH class 181
MBRI-93.02 (hPTH) 181
Unhampered development will allay looming class competition 181
CHAPTER 9 OTHER DRUGS LATE-STAGE ANALYSIS AND FORECASTS 183
Comparative forecasts 183
Comparative Datamonitor drug assessment summaries 183
Overview of 'other drugs' 184
Definition of current comparator therapy 185
Denosumab (AMG-162) 185
Drug profile 185
Clinical trial data 186
Patient potential 189
Marketing potential 189
Satisfaction of unmet needs 191
Forecasts to 2016 191
Datamonitor drug assessment summary 193
ED-71 194
Drug profile 194
Clinical trial data 195
Patient potential 197
Marketing potential 197
Satisfaction of unmet needs 198
Forecasts to 2016 199
Datamonitor drug assessment summary 200
Other drugs in the class 201
MK-0822 201
Merck diversifies to cathepsin K inhibitors in the event of falling bisphosphonate sales 201
NBS-101 202
Clinical and commercial doubt surrounds DABA 202
SHT-546 203
CHAPTER 10 INNOVATIVE EARLY-STAGE PROJECTS 205
Key Phase I compounds in osteoporosis 205
ACE-011 206
Potential to pioneer the provision of anti-resorptive and anabolic activity 206
Changing the face of osteoporosis treatment 206
Acceleron should optimize interest in ACE-011 206
2MD 207
A high risk strategy for Pfizer 207
Early results indicate a potent anabolic agent 207
ED-71's progress represents a useful guide 207
Raloxifene (extended release) 208
A reformulation to rival Evista 208
Proprietary technology improves bioavailability 208
External influences on SERM commercialization must be considered 209
BIBLIOGRAPHY 210
Journal papers and conference abstracts 210
Websites 217
APPENDIX A 220
Methodology 220
Datamonitor forecast methodology 220
Market sizing 220
Estimated 2006 sales revenue 221
Osteoporosis specific sales calculations 221
Product forecasts 221
Estimation of launch dates 222
Definition of a standard unit 222
Japanese market data 222
Patient expiry and generic assumptions 222
Datamonitor drug assessment summary 225
Contributing experts 226
Report methodology 227
APPENDIX B 228
About Datamonitor 228
About Datamonitor Healthcare 228
Datamonitor Healthcare's therapy area capabilities 229
About the Women's Health analysis team 230
Disclaimer 231
List of Tables
Table 1: Forecast key pipeline products for osteoporosis in the seven major markets ($), 2006-2016 5
Table 2: R&D pipeline in osteoporosis, 2007 21
Table 3: Causes of secondary (Type III) osteoporosis 38
Table 4: World Health Organization classification of osteoporotic bone loss 41
Table 5: Epidemiology overview of osteoporosis 52
Table 6: Prevalence of osteopenia and osteoporosis in postmenopausal women across the seven major markets, 2007 53
Table 7: Prevalence of osteopenia and osteoporosis in men over 50 in the seven major markets, 2007 60
Table 8: Prevalence of vertebral fractures in men and women over 50 in the seven major markets, 2007 65
Table 9: UN projected population aged 50 years and over in 2017 69
Table 10: Summary of therapeutic classes in osteoporosis, by ATC code in alphabetical order 81
Table 11: Overview of currently marketed bisphosphonates indicated for use in osteoporosis treatment and prevention, 2007 82
Table 12: Overview of currently marketed SERM indicated for use in osteoporosis treatment and prevention, 2007 86
Table 13: Overview of currently marketed calcitonins indicated for use in osteoporosis treatment and prevention, 2007 87
Table 14: Overview of currently marketed PTH drugs indicated for use in osteoporosis treatment and prevention, 2007 89
Table 15: Overview of currently marketed DABA products indicated for use in osteoporosis treatment and prevention, 2007 91
Table 16: Quantitative measures used for clinical efficacy endpoints in osteoporosis 102
Table 17: Summary of the biochemical markers of bone resorption and formation used to measure rate of bone turnover 106
Table 18: Late-stage bisphosphonates in development for osteoporosis 112
Table 19: Fosamax: key facts 112
Table 20: Defining the gold standard: key clinical trial results for Fosamax 114
Table 21: Novartis's HORIZON trial design, 2003 116
Table 22: Key events, approval and launch dates impacting Aclasta revenue forecasts for osteoporosis in the seven major markets, 2007-2016 124
Table 23: Key events, approval and launch dates impacting Bisponal revenue forecasts for osteoporosis in the seven major markets, 2007-2016 131
Table 24: Key events, approval and launch dates impacting MER-103 revenue forecasts for osteoporosis in the seven major markets, 2007-2016 137
Table 25: Late-stage SERMs in development for osteoporosis 141
Table 26: Evista key facts 142
Table 27: Key events, approval and launch dates impacting bazedoxifene revenue forecasts for osteoporosis in the seven major markets, 2007-2016 151
Table 28: Late-stage calcitonins in development for osteoporosis 156
Table 29: Miacalcin: key facts 157
Table 30: Forthcoming trials for BN-002 159
Table 31: Key events, approval and launch dates impacting BN-002 revenue forecasts for osteoporosis in the seven major markets, 2007-2016 163
Table 32: Late-stage PTH in development for osteoporosis 168
Table 33: Forteo: key facts 168
Table 34: Key events, approval and launch dates impacting hPTH revenue forecasts for osteoporosis in the seven major markets, 2007-2016 173
Table 35: Key events, approval and launch dates impacting Ostabolin-C revenue forecasts for osteoporosis in the seven major markets, 2007-2016 179
Table 36: Other late-stage drugs in development for osteoporosis 185
Table 37: Key events, approval and launch dates impacting Denosumab revenue forecasts for osteoporosis in the seven major markets, 2007-2016 192
Table 38: Key events, approval and launch dates impacting ED-71 revenue forecasts for osteoporosis in the seven major markets, 2007-2016 199
Table 39: Drugs in Phase I and preclinical development for osteoporosis, 2007 205
Table 40: Summary of therapeutic classes in osteoporosis, by ATC code in alphabetical order 220
Table 41: Estimation of launch dates by phase of development 222
Table 42: Estimated generic discounts by country, 2006* 223
Table 43: Estimates of brand erosion by following patent expiry by country 224
Table 44: Weightings of research and clinical factors used for pipeline drug assessment 225
Table 45: Weightings of commercial factors used for pipeline drug assessment 226
List of Figures
Figure 1: Datamonitor's osteoporosis drug assessment summary for the seven major markets, 2007-2016 6
Figure 2: Osteoporosis pipeline breakdown by development phase, 2007 23
Figure 3: The osteoporosis pipeline by phase and class of drug, 2007 24
Figure 4: Osteoporosis drugs and their overlap into other indications 40
Figure 5: Unmet clinical needs in osteoporosis, 2007 71
Figure 6: Unmet environmental needs in osteoporosis, 2007 76
Figure 7: Schematic showing steps of vitamin D activation 95
Figure 8: Datamonitor's comparative forecast of sales for the bisphosphonates across the seven major markets ($m), 2007-2016e 110
Figure 9: Datamonitor's competitive positioning analysis for Aclasta, MER-103 and Bisponal in the seven major markets, 2007-2016 111
Figure 10: Datamonitor's forecast of sales for Aclasta across the seven major markets ($m), 2007-2016 125
Figure 11: Datamonitor's competitive positioning analysis for Aclasta in the seven major markets, 2007-2016 126
Figure 12: Datamonitor's forecast of sales for Bisponal across the seven major markets ($m), 2007-2016 132
Figure 13: Datamonitor's competitive positioning analysis for Bisponal in the seven major markets, 2007-2016 133
Figure 14: Datamonitor's forecast of sales for MER-103 across the seven major markets ($m), 2007-2016 138
Figure 15: Datamonitor's competitive positioning analysis for MER-103 in the seven major markets, 2007-2016 139
Figure 16: Datamonitor's forecast of sales for bazedoxifene across the seven major markets ($m), 2007-2016 152
Figure 17: Datamonitor's competitive positioning analysis for bazedoxifene in the seven major markets, 2007-2016 153
Figure 18: Datamonitor's forecast of sales for BN-002 across the seven major markets ($m), 2007-2016 164
Figure 19: Datamonitor's competitive positioning analysis for BN-002 in the seven major markets, 2007-2016 165
Figure 20: Datamonitor's comparative forecast of sales for PTH across the seven major markets ($m), 2007-2016 166
Figure 21: Datamonitor's competitive positioning analysis for Ostabolin-C and hPTH in the seven major markets, 2007-2016 167
Figure 22: Datamonitor's forecast of sales for hPTH across the seven major markets ($m), 2007-2016 174
Figure 23: Datamonitor's competitive positioning analysis for hPTh in the seven major markets, 2007-2016 175
Figure 24: Datamonitor's forecast of sales for Ostabolin-C across the seven major markets ($m), 2007-2016 180
Figure 25: Datamonitor's competitive positioning analysis for Ostabolin-C in the seven major markets, 2007-2016 181
Figure 26: Datamonitor's comparative forecast of sales for 'other drugs' across the seven major markets ($m), 2007-2016 183
Figure 27: Datamonitor's competitive positioning analysis for Denosumab and ED-71 in the seven major markets, 2007-2016 184
Figure 28: Datamonitor's forecast of sales for Denosumab across the seven major markets ($m), 2007-2016 193
Figure 29: Datamonitor's competitive positioning analysis for Denosumab in the seven major markets, 2007-2016 194
Figure 30: Datamonitor's forecast of sales for ED-71 across the seven major markets ($m), 2007-2016 200
Figure 31: Datamonitor's competitive positioning analysis for ED-71 in the seven major markets, 2007-2016 201