Pipeline Insight: Osteoporosis
Scope
Report Highlights
Reasons to Purchase
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE - page 2
- About the Women's Health pharmaceutical analysis team - page 2
- CHAPTER 1 EXECUTIVE SUMMARY - page 3
- Scope of the analysis - page 3
- Datamonitor insight into the disease osteoporosis market - page 3
- Key metrics - page 6
- Datamonitor Pipeline Assessment Summary - page 7
- CHAPTER 2 PIPELINE OVERVIEW AND FUTURE FOCUS - page 15
- Key conclusions regarding top-line view of pipeline - page 15
- A diverse pipeline ready to burst - page 18
- PTH therapies and reformulations throughout the pipeline - page 19
- A diverse pipeline ready to burst - page 18
- Key companies involved in the osteoporosis pipeline - page 20
- Pfizer - market entry setback as Oporia stumbles at FDA - page 20
- What were the reasons for rejection and what are Pfizer's options? - page 21
- Potential strategic options and impact on Oporia's launch date estimates and future revenues - page 22
- Novartis - page 26
- Missing the bone-formation boat? - page 26
- Patent expiration could leave new indications at risk. Are dosing reformulations enough to protect them? - page 27
- GlaxoSmithKline - A newcomer with a long-term approach - page 29
- Chugai - a major player in Japan - page 30
- Merck - managing the Fosamax lifecycle - page 30
- Merck's line expands, but the patent is wide open - page 31
- Missing long-term investment opportunities - page 33
- Pfizer - market entry setback as Oporia stumbles at FDA - page 20
- Key conclusions regarding top-line view of pipeline - page 15
- CHAPTER 3 PIPELINE DYNAMICS - page 35
- Definition of osteoporosis - page 35
- Etiology of osteoporosis - page 36
- Osteoporosis classification: primary and secondary - page 36
- Pathology and complications - page 37
- Drug targets in osteoporosis - page 38
- Development of osteoporosis drugs - page 39
- Etiology of osteoporosis - page 36
- Epidemiology of osteoporosis - page 41
- Methodological difficulties in assessing prevalence - page 42
- Prevalence of osteoporosis and osteopenia in postmenopausal women - page 44
- Overview of the prevalence of osteoporosis and osteopenia in postmenopausal women - page 44
- US - page 47
- Japan - page 48
- France - page 49
- Germany - page 49
- Italy - page 50
- Spain - page 51
- UK - page 51
- Segmentation of osteoporosis - page 52
- Prevalence of osteoporosis and osteopenia in men - page 52
- Introduction - page 52
- Overview of the prevalence of osteoporosis/osteopenia in men - page 53
- US - page 54
- Japan - page 55
- France - page 55
- Germany - page 56
- Italy - page 56
- Spain - page 56
- UK - page 57
- Osteoporotic fractures, their implications and minor risk groups - page 57
- Introduction - page 57
- Limitations of fracture prevalence data - page 58
- Overview of fracture prevalence - page 58
- US - page 60
- Japan - page 61
- France - page 61
- Germany - page 61
- Italy - page 62
- Spain - page 62
- UK - page 63
- Niche populations - page 64
- Glucocorticoid-induced osteoporosis - page 64
- Anorexia nervosa - page 65
- HIV - page 65
- CNS disorder-related bone loss - page 66
- Paget's disease - page 66
- Ethnic diversity - page 67
- Premature menopause - page 67
- Prevalence of osteoporosis and osteopenia in men - page 52
- Unmet needs in osteoporosis - page 69
- Unmet clinical needs - page 69
- Need for improved compliance - page 69
- Need for efficacy at the hip - BMD and fractures - page 71
- Need for efficacy at the spine - equivalent to Fosamax and Actonel in fractures and BMD - page 71
- Need for additional bone-forming agents - alternative formulations, better safety profile, efficacy at the hip - page 72
- Need for surrogate endpoint efficacy - suppression of resorption and maintenance or up-regulation of formation - page 73
- Unmet environmental needs - page 74
- Need for greater recognition of secondary causes of osteoporosis - page 74
- Need for greater recognition of male osteoporosis and causes of secondary osteoporosis in men for screening or case-finding purposes - page 75
- Need for primary prevention in osteoporosis - preventing the first fracture reduces the future fracture burden - page 76
- Need for increased patient identification, treatment rates and use of appropriate treatments in each patient - page 77
- Unmet clinical needs - page 69
- Definition of osteoporosis - page 35
- CHAPTER 4 R&D APPROACH - page 79
- Classification of pipeline products - page 79
- Bisphosphonates - page 80
- Mechanism of action - page 81
- Class breakdown - page 81
- The gold standard therapy: Fosamax - page 82
- SERMs - page 83
- Mechanism of action - page 84
- Calcitonins - page 84
- Mechanism of action - page 85
- Parathyroid hormone (PTH) and analogues - page 86
- Mechanism of action - page 86
- Hormone therapy - page 87
- Mechanism of action - page 87
- Class breakdown - page 88
- Vitamin D - page 89
- Mechanism of action - page 89
- Bisphosphonates - page 80
- Clinical trial design in osteoporosis - page 90
- Clinical trial guidelines - page 90
- Pre-clinical planning: use of animal models - page 91
- Prevention and treatment: the implications for endpoint selection - page 91
- Trial design and study population - page 92
- Osteoporosis trial design and execution: can anything replace fracture data? - page 93
- Problems with definitions: a need for greater consistency - page 93
- Large-scale trials: can surrogate endpoints ever predict fracture risk? - page 93
- The ethics of placebo-controlled trials: is there a realistic alternative? - page 93
- Recruiting the right study population - page 95
- Clinical trial guidelines - page 90
- Clinical trial endpoints in osteoporosis - page 95
- Fracture rate - page 96
- Significance of fracture rate as an endpoint - page 96
- Considerations with fracture endpoints - page 97
- Changes in BMD - page 98
- Significance of BMD as an endpoint - page 98
- Limitations of BMD as a clinical trial endpoint - page 99
- Biochemical markers of bone turnover - page 100
- How useful are bone markers? - page 101
- Limitations in the use of bone-specific markers - page 101
- Surrogate endpoints: predicting fracture risk - page 102
- Changes in bone microarchitecture - page 102
- Problems associated with microarchitecture assessment - page 103
- Fracture rate - page 96
- Classification of pipeline products - page 79
- CHAPTER 5 BISPHOSPHONATES LATE-STAGE DRUG ANALYSIS & FORECASTS - page 104
- Overview for the bisphosphonates - page 104
- Pipeline summary - page 104
- Definition of current comparator therapy - Fosamax - page 105
- Clinical trial data - page 106
- Fosamax Plus D (alendronate and cholecalciferol) - page 107
- Drug overview - page 107
- Pipeline attractiveness - page 109
- Forecast - page 109
- Drug overview - page 107
- Boniva (ibandronate) - page 110
- Drug overview - page 110
- Clinical trial data - page 111
- Patient potential - page 120
- Marketing factors - page 121
- Satisfaction of unmet needs - page 123
- Pipeline attractiveness - page 127
- Forecasts - page 128
- Drug overview - page 110
- Aclasta (zoledronate) - page 129
- Drug overview - page 129
- Clinical trial data - page 131
- Patient potential - page 132
- Marketing factors - page 135
- Satisfaction of unmet needs - page 136
- Pipeline attractiveness - page 140
- Forecasts - page 141
- Drug overview - page 129
- Comparison of key compounds in the bisphosphonate class - page 142
- Overview for the bisphosphonates - page 104
- CHAPTER 6 SERMS LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 145
- Overview for the SERMs - page 145
- Pipeline summary - page 145
- Definition of current comparator therapy - Evista - page 145
- Comparative analysis - page 147
- Oporia (lasofoxifene) - page 148
- Drug overview - page 148
- Clinical trial data - page 148
- Ongoing late-stage clinical trials - page 154
- Patient potential - page 154
- Marketing factors, ambitious plans for simultaneous global launch - page 156
- Satisfaction of unmet needs - page 157
- Pipeline attractiveness - page 160
- Forecasts - page 161
- Drug overview - page 148
- Bazedoxifene - page 162
- Drug overview - page 162
- Clinical trial data - page 163
- Bazedoxifene and Premarin - page 164
- Patient potential - page 165
- Marketing factors, overcoming negative hormone therapy perceptions - page 166
- Satisfaction of unmet needs - page 167
- Pipeline attractiveness - page 171
- Forecasts - page 172
- Drug overview - page 162
- Comparison of key compounds in the SERM class - page 173
- Overview for the SERMs - page 145
- CHAPTER 7 PTH LATE-STAGE DRUG ANALYSIS - page 176
- Overview for PTH class - page 176
- Pipeline summary - page 176
- Definition of current comparator therapy - Forteo - page 177
- Comparative analysis - page 179
- Preos/Preotact (rhPTH 1-84) - page 179
- Drug overview - page 179
- Clinical trial data - page 179
- Patient potential - page 187
- Marketing factors - page 188
- Satisfaction of unmet needs - page 190
- Pipeline attractiveness - page 193
- Forecasts to 2015 - page 194
- Drug overview - page 179
- Other PTH drugs in development - page 195
- Asahi Kasei Pharma - teriparatide/PTH (1-34) - page 195
- Comparison of key compounds in the PTH class - page 196
- Overview for PTH class - page 176
- CHAPTER 8 CALCITONIN LATE-STAGE DRUG ANALYSIS - page 197
- Overview of the calcitonins - page 197
- Pipeline overview - page 198
- Definition of current comparator therapy - Miacalcin - page 198
- Clinical trial data - page 199
- Comparative analysis - page 200
- Fortical - page 200
- Drug overview - page 200
- Clinical trial data - page 201
- Patient and marketing potential - page 202
- Satisfaction of unmet needs - page 203
- Pipeline attractiveness - page 206
- Forecasts - page 207
- Drug overview - page 200
- Overview of the calcitonins - page 197
- CHAPTER 9 'OTHER DRUGS' LATE-STAGE DRUG ANALYSIS - page 208
- Pipeline Overview - page 208
- Definition of current comparator therapy - page 208
- Comparative analysis - page 209
- Protelos (strontium ranelate) - page 209
- Drug overview - page 209
- Clinical trial data - page 210
- Patient potential - page 217
- Marketing factors - page 218
- Satisfaction of clinical unmet needs - page 219
- Pipeline attractiveness - page 221
- Forecasts - page 223
- Protelos (strontium ranelate) - page 209
- Denusomab (AMG-162) - page 224
- Drug overview - page 224
- Clinical trial data - page 225
- Patient and marketing potential - page 228
- Satisfaction of unmet needs - page 229
- Pipeline attractiveness - page 231
- Forecasts - page 232
- Drug overview - page 224
- ED-71 - page 233
- Drug Overview - page 233
- Clinical trial data - page 234
- Patient and marketing potential - page 236
- Satisfaction of unmet needs - page 237
- Pipeline attractiveness - page 240
- Forecasts - page 241
- Drug Overview - page 233
- Comparison of key compounds in the 'Others' class - page 242
- Pipeline Overview - page 208
- CHAPTER 10 INNOVATIVE EARLY-STAGE PROJECTS - page 245
- Key Preclinical compounds in osteoporosis - page 245
- Src kinase inhibitors - page 247
- Vitronectin receptor antagonists - page 247
- GSK - SB 273005 - page 247
- Long-acting proteins - page 247
- Human Genome Sciences - page 247
- APPENDIX A - page 249
- Methodology - page 249
- Datamonitor forecast methodology - page 249
- Datamonitor drug assessment summary - page 249
- Bibliography - page 249
- Epidemiology - page 249
- United States - page 249
- Japan - page 250
- France - page 250
- Germany - page 251
- Italy - page 251
- Spain - page 252
- UK - page 252
- General - page 253
- Clinical trial data - page 254
- Epidemiology - page 249
- Report methodology - page 255
- Methodology - page 249
- APPENDIX B - page 256
- About Datamonitor - page 256
- About Datamonitor Healthcare - page 256
- Datamonitor Healthcare's therapy area capabilities - page 257
- About the cardiovascular analysis team - page 258
- Disclaimer - page 259
- About Datamonitor - page 256
- List of Tables
- Table 1: Global forecast for top five pipeline drugs and total osteoporosis market ($m), 2005-15 - page 6
- Table 2: Summary of commercial and research/clinical attractiveness of top five late-phase drugs for osteoporosis - page 7
- Table 3: R&D pipeline in osteoporosis, 2005 - page 15
- Table 4: Number of key osteoporosis drugs by class and development phase, 2005 - page 17
- Table 5: Summary of PTH therapies in development for osteoporosis - page 20
- Table 6: Causes of secondary (Type III) osteoporosis - page 37
- Table 7: World Health Organization classification of osteoporotic bone loss - page 42
- Table 8: Epidemiology overview of osteoporosis - page 45
- Table 9: Prevalence of osteopenia and osteoporosis in postmenopausal women across the seven major markets, 2005 - page 46
- Table 10: Prevalence of osteopenia and osteoporosis in men over 50 in the seven major markets, 2005 - page 53
- Table 11: Prevalence of vertebral fractures in men and women over 50 in the seven major markets, 2005 - page 59
- Table 12: Summary of therapeutic classes in osteoporosis, by ATC code in alphabetical order - page 79
- Table 13: Regional patent expiration of currently-marketed osteoporosis drugs - page 80
- Table 14: Overview of currently-marketed bisphosphonates indicated for use in osteoporosis treatment and prevention - page 80
- Table 15: Overview of currently-marketed SERMs indicated for use in osteoporosis treatment and prevention - page 83
- Table 16: Overview of currently-marketed calcitonins indicated for use in osteoporosis treatment - page 85
- Table 17: Overview of currently marketed PTH drugs indicated for use in osteoporosis treatment - page 86
- Table 18: Quantitative measures used for clinical efficacy endpoints in osteoporosis - page 96
- Table 19: Summary of the biochemical markers of bone resorption and formation used to measure rate of bone turnover - page 100
- Table 20: Summary of bisphosphonate products in late-stage development for osteoporosis - page 105
- Table 21: Fosamax: Key facts - page 106
- Table 22: Defining the gold standard: key clinical trial results for Fosamax - page 107
- Table 23: Summary of products within the Fosamax brand - page 108
- Table 24: Dose ranging study results for 20mg and placebo with ibandronate, % change from baseline - page 114
- Table 25: Summary of Phase II trials of ibandronate in postmenopausal osteoporosis - page 115
- Table 26: Results at 2 and 3 years in study comparing 3-monthly i.v. ibandronate, and daily oral alfacalcidol, % BMD relative to baseline, 2003 - page 119
- Table 27: Factors affecting forecast revenues of Boniva (oral and IV), 2005-15 - page 129
- Table 28: Novartis's HORIZON trial design, 2003 - page 130
- Table 29: Factors affecting forecast revenues of Aclasta, 2008-15 - page 141
- Table 30: Global sales forecasts for bisphosphonates, 2005-15 - page 143
- Table 31: SERMs late-stage pipeline summary - page 145
- Table 32: Evista: key facts - page 146
- Table 33: Percentage change in bone turnover markers with lasofoxifene after six months - page 149
- Table 34: Mean percentage change from baseline at 24 months - page 150
- Table 35: Factors affecting forecast revenues of Oporia, 2008-15 - page 162
- Table 36: Factors affecting forecast revenues of bazedoxifene and bazedoxifene/Premarin, 2008-15 - page 173
- Table 37: Global sales forecasts for SERMs, 2007-15 - page 174
- Table 38: Summary of PTH drugs in late-stage development for osteoporosis - page 176
- Table 39: Forteo: key facts - page 178
- Table 40: Results of PATH trial (%), 2003 - page 185
- Table 41: Factors affecting forecast revenues of Preos/Preotact, 2008-15 - page 195
- Table 42: Overview of the calcitonins in late-stage development for the prevention or treatment of osteoporosis - page 198
- Table 43: Miacalcin: key facts - page 199
- Table 44: Factors affecting forecast revenues of Fortical, 2008-15 - page 207
- Table 45: Overview of 'Other' drugs in late-stage development for the prevention and treatment of osteoporosis, 2005 - page 208
- Table 46: Study population, design and endpoints. - page 213
- Table 47: PREVOS change in BMD results, percent from baseline - page 214
- Table 48: STRATOS mean annual change in BMD, percent from baseline - page 214
- Table 49: Factors affecting forecast revenues of Protelos, 2008-15 - page 224
- Table 50: Factors affecting forecast revenues of ED-71, 2008-15 - page 241
- Table 51: Global sales forecasts for 'Other' drugs, 2005-15 - page 243
- Table 52: Drugs in development for osteoporosis, 2005 - page 245
- List of Figures
- Figure 1: Datamonitor osteoporosis drug assessment summary - page 7
- Figure 2: Osteoporosis pipeline breakdown by development phase shows heavily pregnant late-stage pipeline - page 17
- Figure 3: Pipeline overview of osteoporosis drugs - page 18
- Figure 4: Pfizer's possible actions in response to FDA "not approvable" letter on Oporia for osteoporosis prevention - page 24
- Figure 5: US Oporia forecast comparing Datamonitor's potential sales estimates before and after FDA gave its not approvable verdict - page 25
- Figure 6: Forecast of Fosamax brand, generic and total molecule sales in the US, 2004-15 - page 33
- Figure 7: Schematic of key current and pipeline drugs, their targets and their effects on bone formation and resorption - page 39
- Figure 8: Osteoporosis drugs and their overlap into other indications - page 41
- Figure 9: Prevalence of osteopenia and osteoporosis in women over 50 years across the seven major markets, 2005 - page 47
- Figure 10: Prevalence of osteopenia and osteoporosis in men over 50 in the seven major markets, 2005 - page 54
- Figure 11: Prevalence of vertebral fractures in men and women over 50 across the seven major markets, 2005 - page 60
- Figure 12: Unmet clinical needs in osteoporosis - page 69
- Figure 13: Schematic showing steps of vitamin D activation - page 90
- Figure 14: Pipeline attractiveness of Fosamax Plus D/Fosavance in osteoporosis - page 109
- Figure 15: Osteoporosis sales forecast for Fosamax Plus D in osteoporosis to 2015 - page 110
- Figure 16: SWOT analysis of Boniva for osteoporosis - page 125
- Figure 17: Assessment of Boniva key performance indicators - page 126
- Figure 18: Pipeline attractiveness of Boniva in osteoporosis - page 127
- Figure 19: Global sales forecast for Boniva (oral and IV) in osteoporosis to 2015 - page 128
- Figure 20: SWOT analysis of Aclasta for osteoporosis - page 138
- Figure 21: Assessment of Aclasta key performance indicators - page 139
- Figure 22: Pipeline attractiveness of Aclasta in osteoporosis - page 140
- Figure 23: Global sales forecast for Aclasta in osteoporosis to 2015 - page 141
- Figure 24: Datamonitor's drug assessment summary for the late-stage pipeline bisphosphonate therapies - page 142
- Figure 25: Global sales forecasts for bisphosphonates, 2005-15 - page 143
- Figure 26: SWOT analysis of Oporia in osteoporosis - page 158
- Figure 27: Assessment of Oporia key performance indicators - page 159
- Figure 28: Pipeline attractiveness of Oporia for osteoporosis - page 160
- Figure 29: Global sales forecast for Oporia in osteoporosis to 2015 - page 161
- Figure 30: SWOT analysis of bazedoxifene in osteoporosis - page 169
- Figure 31: Assessment of bazedoxifene key performance indicators - page 170
- Figure 32: Pipeline attractiveness of bazedoxifene and bazedoxifene plus Premarin for osteoporosis - page 171
- Figure 33: Global sales forecast for bazedoxifene and bazedoxifene/Premarin in osteoporosis to 2015 - page 172
- Figure 34: Datamonitor's drug assessment summary for the late-stage pipeline SERM therapies - page 173
- Figure 35: Global sales forecasts for SERMs, 2007-15 - page 174
- Figure 36: SWOT analysis of Preos in osteoporosis - page 191
- Figure 37: Assessment of Preos key performance indicators - page 192
- Figure 38: Pipeline attractiveness of Preos for osteoporosis - page 193
- Figure 39: Global sales forecast for Preos/Preotact in osteoporosis to 2015 - page 194
- Figure 40: Datamonitor's drug assessment summary for the late-stage pipeline PTH therapies - page 196
- Figure 41: SWOT analysis of Fortical in osteoporosis - page 204
- Figure 42: Assessment of Fortical key performance indicators - page 205
- Figure 43: Pipeline attractiveness of Fortical for osteoporosis - page 206
- Figure 44: Global sales forecast for Fortical in osteoporosis to 2015 - page 207
- Figure 45: SWOT analysis of Protelos in osteoporosis - page 220
- Figure 46: Assessment of Protelos key performance indicators - page 221
- Figure 47: Pipeline attractiveness of Protelos for osteoporosis - page 222
- Figure 48: Global sales forecast for Protelos in osteoporosis to 2015 - page 223
- Figure 49: SWOT analysis of Denosumab in osteoporosis - page 230
- Figure 50: Assessment of Denosumab key performance indicators - page 231
- Figure 51: Pipeline attractiveness of Denosumab in osteoporosis - page 232
- Figure 52: Global sales forecast for Denosumab in osteoporosis to 2015 - page 233
- Figure 53: SWOT analysis of ED-71 in osteoporosis - page 238
- Figure 54: Assessment of ED-71 key performance indicators - page 239
- Figure 55: Pipeline attractiveness of ED-71 for osteoporosis - page 240
- Figure 56: Global sales forecast for ED-71 in osteoporosis to 2015 - page 241
- Figure 57: Datamonitor's drug assessment summary for the late-stage pipeline 'Other' therapies - page 242
- Figure 58: Global sales forecasts for 'Other' drugs, 2005-15 - page 243
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