Table of Contents

About the Urology and Gender-specific Health pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Market definition for this report 3
Objective of the analysis 3
Strategic scoping and focus 3
Datamonitor insight into the non-hormonal menopause market 4
Contributing experts 5
Related reports 6
CHAPTER 2 PATIENT POTENTIAL 8
Condition definition 9
Symptoms of the menopause 9
Pathogenesis of vasomotor symptoms has not yet been fully elucidated 10
Vasomotor symptoms affect 75% of women over the age of 50 12
Prevalence of vasomotor symptoms is associated with changes in menopausal status 13
There exist ethnic and cultural variations in the prevalence of menopausal symptoms 15
Menopausal symptoms negatively impact quality of life 16
Patient presentation and diagnosis 17
Approximately 60% of symptomatic women seek help with menopausal symptoms 17
Companies developing non-hormonal treatments would benefit from targeting mildly symptomatic patients 18
Diagnosis of menopause is usually made by menstrual and medical history 20
Identifying the target population 21
The average age of onset of natural menopause is 51 years 21
Genetics and cigarette smoking can influence the timing of natural menopause 21
Over 166 million women in the seven major markets are peri- or post-menopausal 23
Approximately 115 million women in the seven major markets will experience menopausal symptoms 23
Over 68 million women will seek treatment for menopausal symptoms in the seven major markets in 2008 24
The target patient population will grow by 34% by 2050 in the seven major markets 26
The proportion of postmenopausal women living in developing nations is set to grow 27
Women aged 45-55 are not the only patients to experience menopausal symptoms 27
Premature ovarian failure occurs in women younger than age 40 27
Premature ovarian failure affects over 1 million women in the seven major markets 28
Surgically induced and medical menopause 29
Breast cancer patients and survivors experience hot flashes 29
CHAPTER 3 CURRENT MARKET SITUATION AND FUTURE POTENTIAL 31
Current treatment options 32
Hormonal therapies are the mainstay of treatment for symptoms of the menopause 32
Complementary and alternative medicine: popular yet lacking in long-term data 32
Efficacy studies of complementary and alternative medicines are inconsistent and inconclusive 34
Professional organizations provide contrasting recommendations regarding use of herbal treatments 35
Non-hormonal treatments are presently prescribed off-label 35
CNS drugs are the most widely prescribed off-label treatments 37
Treatment guidelines acknowledge that non-hormonal alternatives show promise 40
The rationale for a non-hormonal approach to treatment 41
Patients and physicians will welcome non-hormonal menopause treatments 41
Women's Health Initiative identified important risk factors associated with the use of HRT 42
Breast cancer patients and survivors require non-hormonal treatment options due to contraindication of HRT 49
Patients with cardiovascular disorders are also a target population for non-hormonal treatments 50
Market potential of non-hormonal treatments for menopausal symptoms 51
Non-hormonal treatments have the potential to capture at least $535m across the US and 5EU 52
Nevertheless, HRT will remain the mainstay of treatment 53
Prescriber confidence with HRT is slowly returning 53
Patients' ongoing mistrust of HRT represents a market opportunity for non-hormonal treatments 56
CHAPTER 4 R&D PIPELINE OVERVIEW AND CLINICAL TRIAL DESIGN 59
Introduction 60
Historically, antidepressants have been investigated as potential treatments 60
The ideal non-hormonal treatment of menopausal symptoms 62
Pipeline overview 63
Small pipeline consists exclusively of reformulated centrally acting drugs 63
Non-hormonal pipeline is of a comparable size to the HRT pipeline 64
Interest continues in serotonergic mechanisms 65
Wyeth: endeavoring to maintain share of the menopause market 66
Future potential of pipeline non-hormonal treatments for menopausal symptoms 67
Efficacy does not match that of conventional hormonal therapies 67
However, regulatory approval will increase acceptance and prescriber confidence 70
Targeting of co-morbid conditions offers benefit to patients 71
Safety concerns surrounding use of non-hormonals for menopausal symptoms must be addressed 72
Physicians concerns over the long-term safety of antidepressant use in non-depressed women need to be allayed 72
Treatment considerations for breast cancer patients and survivors 73
Stigma surrounding use of antidepressants for a non-psychiatric indication 74
Serotonergic drugs 76
Pristiq (desvenlafaxine) 76
Drug overview 76
Pristiq is set to be the first non-hormonal treatment approved for menopausal symptoms 77
Generic Effexor is unlikely to limit uptake of Pristiq for menopausal symptoms 79
Pristiq - strengths and weaknesses 81
Clinical trial data 82
Org-50081 (esmirtazapine maleate) 86
Drug overview 87
Phase III clinical trial design 87
Datamonitor comments 88
CPT-347 90
Drug overview 90
Datamonitor comments 91
Anticonvulsants 92
Gabapentin GR/Xenolev CR 92
Drug overview 93
Guidelines already recognize gabapentin as an alternative to HRT 93
Reported comparable efficacy between gabapentin and estrogen 94
Gabapentin may be of particular benefit to breast cancer patients 94
Gabapentin GR/Xenolev CR - strengths and weaknesses 95
Clinical trial data 97
Recently discontinued pipeline products 100
Keppra (levetiracetam, injectable) 100
Clinical trial design in non-hormonal treatment research 100
Inclusion and exclusion criteria 101
Primary and secondary endpoints 103
Principal primary endpoint: patient-reported hot flash frequency and severity 103
Secondary endpoint measures 103
Key challenges in menopausal symptom clinical trials 105
Interventions for menopausal symptoms elicit a high placebo response 105
Subjective versus objective measures of vasomotor symptoms 106
BIBLIOGRAPHY 108
Journal papers 108
Websites 119
Datamonitor reports 124
APPENDIX 125
Contributing experts 125
Report methodology 125
Market sizing caveats 125
ATC classes 126
ICD-10 codes 126
Data definitions, limitations and assumptions 127
Standard Units 127
HRT for menopause specific sales calculations 127
About Datamonitor 128
About Datamonitor Healthcare 128
About the Gender-specific Health analysis team 129
Disclaimer 130
List of Tables
Table 1: Prevalence of menopausal symptoms in women aged 40-54 in the 7MM, 2008 12
Table 2: Frequency of menopausal symptoms in a sample of women aged 40-55 years old, by menopausal transition phase 14
Table 3: The potential treatable population for menopausal symptoms across the seven major markets, 2008 23
Table 4: Number of women who experience menopausal symptoms in the menopausal transition period in the seven major markets, 2008 24
Table 5: Number of women seeking treatment for menopausal symptoms in the seven major markets, 2008 25
Table 6: Number of women with premature ovarian failure in the seven major markets , 2008 29
Table 7: Crude female invasive breast cancer incidence rates (per 100,000 persons) in the seven major markets, 2002 49
Table 8: Forecast incidence of invasive female breast cancer in the seven major markets, 2002-17 50
Table 9: Key trials of antidepressant drugs for menopausal symptoms, 2008 60
Table 10: Non-hormonal drugs in development for the treatment of menopausal symptoms, 2008 64
Table 11: Organon/Schering Plough's marketed gynecology and fertility products, 2008 89
Table 12: Primary efficacy outcomes of Gabapentin GR Phase II study 99
List of Figures
Figure 1: Model of the pathogenesis of hot flashes 11
Figure 2: Healthcare seeking behavior for menopausal symptoms 18
Figure 3: Number of women in the menopausal symptoms treatment pathway in the seven major markets, 2008 22
Figure 4: Projection of the female population over 45 years old across the seven major markets, 2005-2050 26
Figure 5: Market share and growth of total off-label non-hormonal prescription market across the seven major markets, 2006-07 36
Figure 6: Sales revenue of key non-hormonal brands prescribed off-label for menopausal symptoms, 2007 39
Figure 7: Timeline of key studies affecting the HRT market 42
Figure 8: Event rates in the Women's Health Initiative study 44
Figure 9: Value of the HRT for menopausal symptoms market in the 6MM, 1999-2007 46
Figure 10: Estimated revenue potential of non-hormonal treatments in the US and 5EU combined, 2007 52
Figure 11: Drugs in the HRT and non-hormonal development pipeline by stage, 2008 65
Figure 12: Comparison of efficacy data of key pipeline drugs and Premarin for vasomotor menopausal symptoms 68
Figure 13: Pristiq: strengths and weaknesses for menopausal symptoms, 2008 81
Figure 14: Gabapentin GR: strengths and weaknesses for menopausal symptoms, 2008 96