Stakeholder Opinions Endometriosis Scientific clarity will unlock market potential

CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Contributing experts 3
Datamonitor insight into the Endometriosis market 4
Related reports 5
CHAPTER 2 MARKET DYNAMICS 7
Endometriosis market definition 8
Limitations in sizing the endometriosis market with IMS data 9
Current market overview 9
Market size has yet to recover from 2006 fall 9
US market changes have contributed to 7MM market shrink 11
Political changes have boosted sales in Spain 12
POCs are the most common treatment option for endometriosis 13
Lupron remains the most popular GnRH agonist treatment 15
CHAPTER 3 DISEASE OVERVIEW 18
Definition of endometriosis 19
Classification of endometriosis: Re-AFS 20
Etiology of endometriosis: still not well understood 22
Retrograde menstruation and implantation 23
Lymphatic/vascular dissemination 23
Developmental coelomic metaplasia 24
Genetic predisposition 24
Environmental factors 25
Immunological susceptibility 25
Dynamic progression of endometriosis 26
Recurrence in endometriosis 27
Symptoms of endometriosis 27
Epidemiology of endometriosis 29
Socio-demographic contributors to endometriosis prevalence 29
Limitations of endometriosis epidemiology analysis 30
Factors specific to endometriosis: 30
Factors generalized to all epidemiology analysis: 32
The gold standard endometriosis epidemiology study 32
Prevalence estimates: the general versus gynecologic population 33
Prevalence of endometriosis in the general population is assumed to be 10% 35
Prevalence of endometriosis in the gynecologic population may be more representational 35
Unmet need in endometriosis 42
Understanding the etiology of endometriosis will aid the development of prophylactic and specific treatments 43
Non-invasive diagnostic procedures will lower morbidity 45
Physician education will quicken time to diagnosis 46
Patient education promotes treatment seeking 47
Better pain management concepts will help women cope 47
CHAPTER 4 TREATMENT TRENDS 49
Endometriosis patient diagnosis and referral algorithm 50
'Under-diagnosed and over treated' 50
Treatment of endometriosis 51
Combined oral contraceptives: first-line therapy 53
Short term efficacy is similar to that of GnRH agonists 53
Progestogen treatments are most commonly used therapy 55
Antiprogestogen use is limited to gestrinone 56
Androgens: Danazol-first treatment indicated for endometriosis 57
Efficacious for pain relief 58
Side effects limit usefulness of product 59
Danazol remains useful for niche patients 60
GnRH agonists: short-term efficacy at the expense of side effects 61
Characteristics of successfully marketed GnRH agonists 62
Lupron: the 'gold standard' 64
Lupron with add-back makes side effects more manageable 66
Surgery for severe and non-responsive endometriosis 68
Laparoscopic surgery: a range of techniques can reduce pain 68
Hysterectomy: the last treatment option 69
Patient treatment goals 69
Pain reduction 70
Pregnancy 71
CHAPTER 5 RESEARCH AND DEVELOPMENT 73
The ideal drug for the treatment of endometriosis 74
Efficacy must prevent recurrence 74
Safety essential in a young patient population 75
Side-effects profile must be improve compliance 75
Cost must be kept low for long-term use 76
Pipeline overview 77
Considerable variety in mechanism, delivery mode, and manufacturer 77
Large pipeline is beginning to mature 79
New methods of drug delivery attempt to fulfill unmet need 80
Nasal administration may be hindered by unwelcome irritation 81
Vaginal route unpopular in conservative patient population 81
Late-stage products offer some hope to patients 82
Visanne progestogen could benefit from specific endometriosis label 82
Balance will need marketing partner to realize Libra's full potential 84
FP-1096 benefits from a novel drug delivery technique 85
Mechanisms of action of pipeline products 86
Aromatase inhibitors may offer long-term remission 88
Chemokine receptor antagonists center on inflammatory and immune response 88
Immunomodulators are still regarded warily 89
Combination products will not radically alter treatment 89
Promising estrogen receptor beta agonists require more research 90
GnRH antagonists have important advantages over agonists 91
Progestogen agonists are as effective as marketed therapies 93
Selective progestogen receptor modulators 94
Clinical trial design in endometriosis 95
Difficulties inherent in clinical trials of endometriosis therapies 95
Patient recruitment must be carefully considered 97
Endpoints in clinical trial design 98
Arguably pain is the endpoint of most relevance to the patient 98
That lesion size should be a secondary endpoint is a contentious issue 99
Quality of life scale expands on the endpoint of pain 100
CHAPTER 6 CURRENT MARKET ISSUES 102
Raising the profile of endometriosis 103
Breaking the taboo 103
Raising awareness: lessons from other disease areas 104
The EEA takes the lead in lobbying in Europe 105
Current issues in diagnosis of endometriosis 107
Biomolecular and genetic diagnostics are desirable but not trusted 108
Current research 108
CA-125 testing has had a mixed response 109
Imaging diagnostics currently offer the most promise 111
The endometriosis indication 112
Physicians find specific labeling increasingly useful 114
The potential of endometriosis as a secondary indication 114
Uterine fibroids 115
Menorrhagia (excessive bleeding) 116
BIBLIOGRAPHY 117
Journal papers 117
Websites 127
APPENDIX 130
IMS data 130
Medical sales data caveats 130
Medical sales data methodology 130
Contributing experts 131
About Datamonitor 131
About Datamonitor Healthcare 131
Datamonitor Healthcare's therapy area capabilities 132
About the Disease analysis team 133
Disclaimer 134
List of Tables
Table 1: ICD-10 codes used to define the endometriosis market 8
Table 2: Frequency and location of endometriosis implants in the pelvis 20
Table 3: Frequency of symptoms among surgically diagnosed endometriosis patients, 2007 28
Table 4: Common symptoms of endometriosis and other conditions 29
Table 5: Epidemiology overview of endometriosis, 2007 34
Table 6: Endometriosis prevalence in the 7MM general population, 2007 35
Table 7: Endometriosis prevalence in the CPP (gynecological) population, 2007 37
Table 8: Endometriosis prevalence in the infertile (gynecologic) population across the seven major markets, 2007 41
Table 9: Summary of endometriosis treatment with danazol 58
Table 10: Endometriosis-specific sales of GnRH agonists in the seven major markets combined, by molecule, 2006-07 62
Table 11: Cost of select GnRH agonists in the UK, 2007 63
Table 12: Lupron product range, 2007 64
Table 13: Overview of the endometriosis pipeline, 2007 77
Table 14: Mechanism of action of the drugs in the endometriosis pipeline, 2007 87
Table 15: Action taken by the European Endometriosis Alliance in H1, 2007 106
List of Figures
Figure 1: The seven major endometriosis markets by country, 2003-07 10
Figure 2: The five major European (EU) endometriosis markets. 2003-07. 11
Figure 3: Seven major endometriosis market size, split by region, 2003--07 12
Figure 4: Volume sales of products within endometriosis treatment types in the seven major markets combined, 2007 14
Figure 5: Market share and market growth of key GnRH agonists in the seven major endometriosis markets, 2006-07 16
Figure 6: Prevalence of CPP and endometriosis in the female population and prevalence of endometriosis in the CPP population (000s), 2007 38
Figure 7: Causes of infertility for US couples undergoing assisted reproductive technology using fresh, non-donor eggs or embryos, 2004 40
Figure 8: Prevalence of infertility and endometriosis in the female population and prevalence of endometriosis in the infertile population (000s), 2007 42
Figure 9: Unmet needs in endometriosis as identified by key opinion leaders, 2007 43
Figure 10: Patient diagnosis referral pathway in endometriosis, according to key opinion leaders, 2007 51
Figure 11: Side-effect versus efficacy profile of key treatments on the endometriosis market according to interviewed EU and US opinion leaders, 2007 52
Figure 12: An endometriosis patient treatment pathway dependent on treatment goal 70
Figure 13: Frequency of products in the pipeline, by development stage, 2007 79
Figure 14: Breakdown of pipeline products by delivery method, where known, in 2007 80