Table of Contents

ABOUT DATAMONITOR HEALTHCARE 2
About the Urology and Gender-specific Health pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Objective of the analysis 3
Datamonitor insight into the hormone replacement therapy (HRT) market 3
Contributing experts 4
Related reports 6
Upcoming related reports 6
CHAPTER 2 MARKET DEFINITION AND OVERVIEW 8
Market definition for this report 9
ATC classes 9
ICD-10 codes 9
IMS sales data 9
Research and development 10
Strategic scoping and focus 10
Disease overview 11
Symptoms of the menopause 12
The impact of symptoms on quality of life 15
The impact of symptoms and treatment seeking 15
Premature ovarian failure 16
Surgically induced and medical menopause 16
Identifying the target population 17
Over 166 million women in the 7MM are peri- or postmenopausal 18
Approximately 115 million women in the 7MM will experience menopausal symptoms 18
Over 68 million women will seek treatment for menopausal symptoms in the 7MM 19
Premature ovarian failure affects over 1 million women in the 7MM 21
Treatment options 21
Treatment guidelines 22
US - AACE menopause guidelines 22
EU - MHRA guidelines 23
Contraindications to HRT 24
Estrogen only preparations 24
Estrogen and progestogen preparations 26
Topical sex hormones 28
CHAPTER 3 GLOBAL MARKET ASSESSMENT 30
Current market situation 31
WHI-induced market decline stabilizes at $1.5 billion in 2007 31
Despite an increase in market value from 2006-07, volume sales continued to fall 32
Small price increases lessen the impact of falling volume sales 33
US market sales account for 85% of the total 7MM revenue 34
Germany is the largest and most robust of the EU markets 35
Majority of the seven major markets show growth in 2007 36
Spanish market leads the way in recuperating losses 37
Estrogen only preparations generate highest revenue 37
Wyeth products still hold the first and second market position 38
2006-07 sales performance of the top 10 HRT brands for menopausal symptoms 39
2006-07 sales performance of the top 10 HRT brands for menopausal symptoms, by class 40
Market opportunity and threats 42
Opportunities 43
An ageing and changing population structure grows the treatable population 43
New variety in market will facilitate shift in treatment paradigms 45
Threats 47
Competition from non-hormonal treatments for menopause 47
The boom of the so-called 'bio-identical' hormone market 49
Poor dissemination of subsequent HRT research by the media 50
Unmet need in the HRT market 53
New mechanism of actions could revolutionize HRT 54
Raising the profile of HRT will expand the treatable population 56
Physician education across specialties will standardize knowledge 57
A measure of dose suitability will facilitate individualized therapy 58
CHAPTER 4 R&D PIPELINE OVERVIEW AND CLINICAL TRIAL DESIGN 61
Pipeline overview: old lifecycle management strategies give way to fundamental changes 62
Aprela's launch will begin the restoration of the market 63
Companies unwilling to invest heavily in HRT research and development 63
Bayer Schering aims to maintain its position in Women's Health 64
Brand loyalty created by commitment to market will overcome pipeline weakness 65
Short-term pipeline strategies have already been exploited 66
Products with an alternative delivery method are limited to a patient subset 66
Low-dose reformulation was an essential yet unsustainable strategy 67
Novel mechanisms of action could radically alter the HRT market 68
Head-to-head trials will help new compounds to reach their full potential 70
The first drug to market: Divigel (estradiol) 71
Forecasts to 2017 71
Divigel: capable of a competitive price point 72
Out-licensing is a key strategy for Orion 73
Patient share will depend on exact labeling approved in Japan 74
Clinical trial design in HRT research 75
FDA revised guidelines 75
Estrogen only drugs 75
Estrogen plus progestogen drugs 76
European Medicine Agency guidelines 78
Efficacy: treatment of symptoms related to estrogen deficiency 78
Safety: endometrial safety 79
Secondary safety endpoints 79
CHAPTER 5 ESTROGEN AGONISTS LATE STAGE DRUG ANALYSIS & FORECASTS 81
Overview for the estrogen agonists 82
Comparative forecasts 82
Comparative Datamonitor drug assessment summary 83
Current comparator therapy: Premarin 84
Premarin, Prempro and the WHI study 86
The damning results of the WHI - HRT linked to serious cardiovascular events and cancer 87
HRT use fell substantially as a result 87
Methodological inaccuracies in the WHI since revealed 88
Key clinical trials: the HOPE study 90
Effects on vasomotor symptoms 90
Efficacy on vulvar and vaginal atrophy 91
Effect on bone mineral density 91
Marketing and patient factors 91
Evamist (estradiol) 94
Drug overview 94
Forecasts to 2017 95
Datamonitor drug assessment 95
Patient potential 96
Marketing factors 97
Evamist will benefit from specialist manufacturers throughout development 97
Clinical trials 98
Aprela (estradiol, bazedoxifene) 99
Drug overview 99
Forecasts to 2017 99
Datamonitor drug assessment 100
Patient potential 101
SERMs and TSECs could revolutionize treatment of menopausal symptoms 101
Marketing factors 102
Large gains to be made if pathway to approval can be smoothed 102
Clinical trial data 104
Clinical trial 1 104
Clinical trial 2 105
MF-101 (estradiol) 105
Drug overview 105
Forecasts to 2017 107
Datamonitor drug assessment 108
Patient potential 108
New mechanism of action stirs excitement over potentially improved safety 108
Marketing factors 109
Bionovo's portfolio will strengthen in the long term 109
Clinical trial data 110
232802 111
Drug overview 111
Marketing and patient factors 111
GSK branches into Women's Health 111
Clinical trial data 112
Phase II trial methodology 112
CHAPTER 6 ESTROGEN AND PROGESTOGEN AGONISTS LATE STAGE DRUG ANALYSIS & FORECASTS 114
Overview for the estrogen and progestogen agonists 115
Comparative forecasts 115
Comparative Datamonitor drug assessment summary 116
Definition of current comparator therapy: Prempro 116
Prempro's key clinical trials 119
The WHI findings 119
Key clinical trials: the HOPE study 120
Effects on vasomotor symptoms 120
Effects on vulvar and vaginal atrophy 120
Effects on the endometrium 120
Effects on bone mineral density 121
Marketing and patient factors 122
Angeliq low-low (ethinyl estradiol, drospirenone) 122
Drug overview 122
Forecasts to 2017 122
Datamonitor drug assessment 123
Patient potential 124
Marketing factors 125
Strong marketing support cannot help if patients are refractory to treatment 125
CHAPTER 7 FORECAST ANALYSIS 126
Key events 126
New product launches in the 7MM 127
Evamist: chosen launch market has most latent potential 128
Angeliq low-low: useful strategy to combat Angeliq generics 128
Aprela: strong uptake in time 129
MF-101: battling Aprela in the US 130
Patent expiries in the 7MM 130
FemHRT (ethinyl estradiol, norethindrone acetate) 132
Activelle (estradiol, norethindrone acetate) 132
Estalis (estradiol, norethisterone acetate) 133
Prempro (CEE, medroxyprogesterone acetate) 133
Angeliq (estradiol, drospirenone) 134
Prices and pricing assumptions 134
Product positioning 135
Datamonitor's pipeline drug assessment model 135
BIBLIOGRAPHY 137
Journal papers 137
Websites 140
APPENDIX 145
Contributing experts 145
Report methodology 145
Datamonitor's drug assessment summary 145
Data definitions, limitations and assumptions 147
Standard Units 147
Estimated 2007 sales revenue 147
HRT for menopause specific sales calculations 147
Derivation of sales forecasts and pricing trends 148
Estimation of launch dates 148
Forecasts 148
Japanese Market Data 148
About Datamonitor 149
About Datamonitor Healthcare 149
About the Gender-specific Health analysis team 150
Disclaimer 151
List of Tables
Table 1: Frequency of menopausal symptoms in a sample of women aged 40-55 years old, by menopausal transition phase 14
Table 2: The potential treatable population for menopausal symptoms, in the 7MM, 2008? 18
Table 3: The number of women who experience menopausal symptoms in the menopausal transition period, in the 7MM, 2008 19
Table 4: The number of women seeking treatment for menopausal symptoms, in the 7MM, 2008 20
Table 5: Number of women in the 7MM with POF, 2008 21
Table 6: The top 10 products, by 2007 sales, in the 7MM HRT market 22
Table 7: Sales of estrogen only preparations used for the treatment of menopausal symptoms in the 7MM, 2007 26
Table 8: Sales of estrogen and progestogen preparations of HRT used for the treatment of menopausal symptoms in the 7MM, 2007 28
Table 9: Sales of topical sex hormones used for the treatment of menopausal symptoms in the 7MM, 2007 29
Table 10: Summary of key opportunities and threats in the HRT market across the 7MM, 2007 43
Table 11: Novel non-hormonal agents in development for the potential treatment of menopausal symptoms, 2008 48
Table 12: Pipeline products in development as HRT for menopausal symptoms, 2008 62
Table 13: Bayer Schering's brand revenue from the HRT market for menopausal symptoms (excluding osteoporosis), 2007 65
Table 14: Key estrogen agonist products in late-stage R&D pipeline for the treatment of menopausal symptoms, 2008 82
Table 15: Premarin: key facts 86
Table 16: Key estrogen and progestogen agonist products in late-stage R&D pipeline for the treatment of menopausal symptoms, 2008 115
Table 17: Prempro: key facts 119
Table 18: Datamonitor's launch dates for HRT products in the US, 5EU and Japanese market, 2008-2017 127
Table 19: Expiry dates for HRT products in the US, 5EU and Japanese market, 2008-2017 131
Table 20: Datamonitor's prices per standard unit and pricing assumptions of the forecast pipeline products, 2008 135
Table 21: Datamonitor's 'research and clinical' drug assessment parameters 146
Table 22: Datamonitor's 'commerical drug assessment parameters 146
Table 23: Estimation of launch dates by phase of development 148
List of Figures
Figure 1: The menopausal transition 12
Figure 2: Frequency of menopausal symptoms in a sample of women aged 40-55 years old 13
Figure 3: Number of women in the 7MM menopausal symptoms treatment pathway, 2008 17
Figure 4: Value of the HRT for menopausal symptoms market in the 7MM, 2003-07 31
Figure 5: Volume sales of HRT products by class in the 7MM combined, 2003-07 32
Figure 6: Value sales of HRT products, by class, in the 7MM combined, 2003-07 34
Figure 7: Value of the HRT for menopausal symptoms market in the 5EU and Japan, 2003-07f 35
Figure 8: Year-on-year growth for HRT for menopausal symptoms in the 7MM, 2003-07f for 36
Figure 9: Market share and market growth of the HRT markets in the 7MM, 2006-07 37
Figure 10: Sales of HRT products for menopausal symptoms by class in the 7MM, 2007 38
Figure 11: Sales performance of the top 10 HRT brands for menopausal symptoms in the 7MM, 2006--07 39
Figure 12: Sales performance of key estrogen only (G3E) HRT brands in the 7MM, 2006-07 40
Figure 13: Sales performance of key estrogen and progestogen (G3F) HRT brands in the 7MM, 2006--07 41
Figure 14: Sales performance of key topical sex hormone (G2F) HRT brands in the 7MM, 2006--07 42
Figure 15: Number of women (million) aged 45 years and above in the 7MM, 2007 and 2017 44
Figure 16: The potential threat of new mechanisms of action on the existing HRT market 49
Figure 17: Google trend analysis of media coverage of 'WHI' from 2005-08. 51
Figure 18: Unmet need in the HRT market according to opinion leaders, 2008 54
Figure 19: Drugs in the HRT development pipeline by stage, 2008 63
Figure 20: Drugs in the HRT development pipeline by mechanism of action, 2008 69
Figure 21: Datamonitor's forecast of sales for Divigel in Japan 2007f-2017 72
Figure 22: Datamonitor's sales forecast for estrogen agonists for the treatment of menopausal symptoms across the 7MM, 2007-2017 83
Figure 23: Datamonitor's competitive positioning analysis for Premarin, Aprela, MF-101 and Evamist in the 7MM, 2008-2017 84
Figure 24: The Wyeth Prem Range, 2008 92
Figure 25: Total promotional spend for the Prem range in the US, 1999-2006 93
Figure 26: Datamonitor's sales forecast of Evamist across the 7MM($m), 2007-2017 95
Figure 27: Datamonitor's competitive positioning analysis for Evamist, relative to Premarin in the 7MM, 2008-2017 96
Figure 28: Datamonitor's forecast of sales for Aprela across the 7MM 7MM($m), 2007-2017 100
Figure 29: Datamonitor's competitive positioning analysis for Aprela, relative to Premarin in the 7MM, 2008-2017 101
Figure 30: Datamonitor's forecast of sales for MF-101 across the 7MM ($m), 2007-2017 107
Figure 31: Datamonitor's competitive positioning analysis for MF-101, relative to Premarin in the 7MM7MM, 2008-2017 108
Figure 32: Datamonitor's comparative forecast of sales for the estrogen and progestogen agonists for the treatment of menopausal symptoms across the 7MM ($m), 2007-2017 115
Figure 33: Datamonitor's competitive positioning analysis for Prempro, and Angeliq low-low in the 7MM, 2008-2017 116
Figure 34: Volume and values sales of Prempro in the 7MM, 2003-07 118
Figure 35: Datamonitor's forecast of sales for Angeliq low-low across the 7MM ($m), 2007-2017 123
Figure 36: Datamonitor's competitive positioning analysis for Angeliq low-low, relative to Prempro, in the seven major markets, 2008-2017 124
Figure 37: Impact of key events on the HRT market for menopausal symptoms, 2008-2017 126
Figure 38: Datamonitor's pipeline assessment model for forecast products in the HRT for menopausal symptoms market, 2008 136