Market Report Source

Overview

Introduction
The market for infertility drugs is a complex and dynamic arena shaped by numerous factors such as changing social attitudes, national legislation, and prescriber preferences. Brand strength and diverse portfolios have allowed Organon, Merck Serono and Ferring to secure a firm foothold in the market, worth over $1 billion in 2006, and represent tough competition.

Scope of this report

• Analysis of patient potential, unmet needs, market dynamics, and clinical trial design in infertility, supported by opinion leader comment
• Assessment of pipeline drugs and future treatment trends and their impact on prescribing patterns and behavior
• Patient based and sales based market forecasts to 2016, the latter providing a breakdown by region, drug class, marketed brands and pipeline drugs
• Coverage of emerging infertility markets which, in light of reproductive tourism, may offer revenue growth potential

Research and analysis highlights
Key differentiators will permit Organon’s Org-36286 (corifollitropin alpha) and Merck Serono’s Pergoveris (r-FSH and r-LH), to cannibalize some share from their proprietors’ franchise leading therapies. However, these agents do not appear to satisfy unmet need and this will prevent sales from rivaling Puregon and Menopur (hMG).

The lack of education of non-specialist physicians limits the number of women receiving treatment. It should be a primary goal of the market to make these doctors more knowledgeable and to implement incentives to encourage patient referral.

New opportunities exist in the development of products to support embryological techniques; cryopreservation, microarrays and in vitro maturation. These procedures will expand the treatable patient population as all women with the intention of preserving and protecting embryos will be eligible for treatment, not just those that are infertile.

Key reasons to read this report

• Quantify the future size of the infertility market and the number of women eligible for infertility treatment to 2016 in the US, 5EU, and Japan
• Understand unmet needs and opportunities in the infertility market based on key opinion leader comments
• Benchmark key late-stage infertility compounds against current market leading brands

Table of Contents

CHAPTER 1 EXECUTIVE SUMMARY 3

Scope of the analysis 3

Contributing experts 4

Datamonitor insight into the infertility market 6

Key metrics 8

Datamonitor pipeline assessment summary 9

CHAPTER 2 DISEASE OVERVIEW 12

Definition of infertility 13

Unassisted reproduction 13

Etiology of infertility 14

The causes of female infertility 14

Polycystic ovary syndrome 15

Endometriosis 17

Uterine fibroids 18

The causes of male infertility 19

Correctable conditions in the male 20

Combined infertility 21

Unexplained infertility 22

CHAPTER 3 EPIDEMIOLOGY AND PATIENT BASED MARKET FORECASTS 23

Epidemiologically-derived infertility market size 24

Epidemiologic methodology of sizing the US and 5EU patient population 24

Female population eligible for infertility treatment (1) 25

Relationship status: marriage assumed necessary (2) 25

Prevalence of infertility (3) 26

Presentation rates (4) 27

Diagnosis rates of a specialist physician (5) 28

Treatment initiation (6) 29

Epidemiologic methodology of sizing the Japanese patient population 30

Patient derived infertility market forecasts 30

Patient derived forecast methodology 32

Trending the treatment seeking rate 32

Trending the marriage rate 32

Segmentation of the patient population by treatment cycles 33

Cost per treatment cycle 34

Market value 34

Epidemiological trends 35

The ageing population will prevent dramatic market growth 35

The prevalence of infertility by etiology 37

Almost 20% of couples seeking treatment require therapy for multiple-factor infertility 38

CHAPTER 4 TREATMENT OPTIONS AND TRENDS 40

Segmentation of infertility treatment 41

ART treatment options 41

Ovulation induction 41

Intrauterine insemination 42

In vitro fertilization 43

Intracytoplasmic sperm injection 44

Gamete intrafallopian transfer 44

Zygote intrafallopian transfer 44

Classification of infertility products 44

Follicle stimulating hormones-follitropins (FSH) 46

Luteinizing hormone (LH) 47

Human menopausal gonadotrophins-menotropins (hMG) 47

Human chorionic gonadotrophin (hCG) 48

Gonadotrophin releasing hormone (GnRH) analogs 49

Pharmaceutical treatment pathways 50

Over 193,000 treatment cycles occurred in the 5EU in 2001 52

Future treatment trends 52

IVF more frequently chosen as first-line therapy 53

GnRH agonists versus GnRH antagonists 54

The advantages of antagonists 55

Efficacy studies fail to identify superior analog 55

Physician choice will divide future market share equally 56

Volume reduction as mild stimulation protocols strive to reduce multiple births 57

Urinary and recombinant products must fulfill different niches 59

r-FSH versus menotropins 61

Unmet need in the infertility market 62

Education of non-specialist physicians will aid diagnosis and referral 63

Complicated treatment cycles detract from success rates 64

Patient-friendly delivery devices help to prevent discontinuation 64

Simplified treatment regimens ease patient stress levels 66

Neutrality in clinical trials to avoid bias 67

CHAPTER 5 MARKET DYNAMICS 69

Market sizing using prescription data 70

Dynamics of the current infertility market 71

Slow growth recoups market value to 2003 level 71

Gonadotrophins are the integral part of infertility treatment 72

GnRH antagonists gain on agonists in 2006 but still have some way to go 74

Regional sales are influenced by country-specific legislation 74

Follitropin products lead the market 77

Product use is not exclusive to infertility 79

Key companies involved in the infertility market 80

Three companies hold 84.6% share of the total infertility market 80

Change at the top means competition will be fierce 81

Smaller portfolios suit current market climate 82

Successful companies generate strong relationships with physicians 82

Organon capitalizes on Puregon to become 2006 market leader 83

Merck Serono loses share despite extensive portfolio 85

Innovation allows Ferring greatest growth 88

IBSA’s geographical experience is a threat to 7MM players 90

SWOT analysis of the infertility market 91

Opportunities 92

Trend towards later parenthood will increase demand for fertility services 92

New embryological techniques expand treatable population 93

Infertility support websites can increase brand awareness among patients 96

Threats 99

Restrictive guidelines are unlikely to slacken in the near future 99

Influx of low-priced alternatives will increase price competition 100

CHAPTER 6 R&D PIPELINE OVERVIEW AND CLINICAL TRIAL DESIGN 104

Pipeline overview: limited pipeline dominated by existing market players 105

Infertility pipeline lacks direction and innovation 106

Development needs to diversify 107

Pergoveris is the initial threat to marketed products 108

Top three market players overwhelm pipeline 108

Merck Serono’s pipeline structure optimizes timing of market entry 109

Organon’s pipeline indicates long-term focus 109

Small companies should capitalize on outlicensing 109

Clinical trial design in infertility and subfertility research 110

Code of best practice 110

Analysis must stem from ‘intention to treat’ patient numbers 111

Controversial crossover trials may inflate results 112

First-cycle enrolment avoids carry-over effects 113

Sample size estimation to be derived from patient number 113

Lack of superiority is not the same as equivalence 114

Should singleton live birth rate replace live birth rate as primary outcome? 114

CHAPTER 7 FOLLITROPIN LATE-STAGE DRUG ANALYSIS & FORECASTS 116

Overview for the follitropin class 117

Comparative forecasts 117

Comparative Datamonitor drug assessment summary 118

Definition of current comparator therapy: Puregon 119

Puregon’s key clinical trials 121

Marketing and patient factors 123

Org-36286 (extended-release corifollitropin alpha) 125

Drug overview 125

Datamonitor drug assessment summary 126

Forecasts to 2016 126

Marketing factors 128

Patient potential 128

Clinical trial data 130

Phase III 130

Phase II 131

CHAPTER 8 MENOTROPIN LATE-STAGE DRUG ANALYSIS & FORECASTS 133

Overview for the menotropin class 134

Comparative forecasts 134

Comparative Datamonitor drug assessment summary 135

Definition of current comparator therapy: Menopur 136

Menopur’s key clinical trials 137

Marketing and patient factors 138

Pergoveris (follitropin alpha and lutropin alpha) 140

Drug overview 140

Datamonitor drug assessment summary 140

Forecasts to 2016 141

Marketing factors 143

Patient potential 144

Clinical trial data 145

Primary Phase II/III bridging study 145

Secondary Phase II/III bridging study 147

CHAPTER 9 GLOBAL MARKET ISSUES 149

Globalization of the infertility market 150

E7 markets are a useful guide to worldwide market growth 150

Despite growth, E7 markets will not rival 7MM in the short term 151

Inter-market differences: the impact of legislation 151

Reproductive tourism 155

A multitude of inter-related factors promote reproductive tourism 156

Case study: Observing patient migration from Italy 157

Responding to the impact of reproductive tourism 158

Pharma must strengthen portfolios in stable or recipient markets 158

Physician behavior is vital to maintain the respectability of reproductive travel 159

Reproductive tourism is the best solution for patients in the absence of ethical agreement 161

BIBLIOGRAPHY 163

Journal papers and articles 163

Websites 168

APPENDIX A 173

Forecasting methodology 173

Datamonitor forecast methodology 173

Epidemiological patient-based forecasts 173

IMS forecasts 175

Contributing experts 177

APPENDIX B 178

About Datamonitor 178

About Datamonitor Healthcare 178

Datamonitor Healthcare’s therapy area capabilities 179

About the Disease analysis team 180

Disclaimer 181

List of Tables

Table 1: Infertility market top down forecast across the seven major markets, 2006-2016 8

Table 2: Top down forecast of key pipeline infertility products in 2016 ($000s) 8

Table 3: Infertility market bottom-up forecast based on patient numbers in the US, Japan and 5EU, 2006-2016 9

Table 4: Causes of female infertility 14

Table 5: Causes of male infertility 19

Table 6: Patient population of women receiving infertility treatment in the 7MM, 2006 24

Table 7: Infertility market value ($m) patient based forecasts, 2003-2009 31

Table 8: Infertility market value ($m) forecast derived from patient numbers, 2010-2016 32

Table 9: Patient numbers by female infertility etiology in the US and 5EU, 2006 39

Table 10: Classification of the infertility market according to Datamonitor’s definition 45

Table 11: Branded follitropins available in the 7MM, 2006 47

Table 12: Branded menotropins available in the 7MM, 2006 48

Table 13: Branded chorionic gonadotrophins available in the 7MM, 2006 49

Table 14: Branded GnRH agonists available in the 7MM, 2006 50

Table 15: Branded GnRH antagonists available in the 7MM, 2006 50

Table 16: Treatment cycles in the 7MM, 2000 and 2001 52

Table 17: Studies investigating the efficacy of GnRH analogs 56

Table 18: ICD-10 codes used to define the infertility market 70

Table 19: Country-specific ART practices, 2007 75

Table 20: Organon’s infertility franchise, 2007 83

Table 21: Merck Serono’s infertility franchise, 2007 86

Table 22: Ferring’s infertility franchise, 2006 88

Table 23: IBSA’s infertility franchise, 2007 90

Table 24: Infertility patient websites, 2007 97

Table 25: Legislation governing ART in the 7MM, 2007 99

Table 26: Infertility market pipeline, 2007 105

Table 27: Key companies involved in the infertility pipeline, 2007 108

Table 28: Methodological considerations of infertility trials 111

Table 29: Key products in late-stage R&D pipeline for follitropins, 2007 117

Table 30: Puregon: key facts 121

Table 31: Key products in late-stage R&D pipeline for menotropins, 2007 134

Table 32: Menopur: key facts 137

Table 33: E7 infertility market sales, 2006 and CAGR, 2003-06 151

Table 34: E7 infertility markets: key facts, 2007 153

Table 35: Datamonitor drug assessment parameters 176

List of Figures

Figure 1: Datamonitor pipeline infertility drug assessment summary 10

Figure 2: Algorithm for the treatment of male infertility 20

Figure 3: Number of women aged between 20 and 45 years old in the seven major infertility markets, 2006-2021 36

Figure 4: Females patients willing and able to receive infertility treatment in the 7MM from 2006 to 2016 37

Figure 5: Causes of infertility for US couples undergoing ART using fresh, non-donor eggs or embryos, 2004 38

Figure 6: ART treatment options 41

Figure 7: Infertility treatment pathway in the seven major markets 51

Figure 8: Schematic overview of trends expected in infertility treatment, 2007-2016 53

Figure 9: Unmet need in the infertility market, 2007 62

Figure 10: Growth of the seven major infertility markets, 2003-06 71

Figure 11: Breakdown of the gonadotrophin class by molecule, 2006 73

Figure 12: Infertility market size by country, 2003-06 76

Figure 13: Sales performance of the top five infertility brands across the 7MM, 2005-06 78

Figure 14: Percentage breakdown of total brand sales by indication of the top five infertility products in the 7MM, 2006 80

Figure 15: Market share and growth of the top three companies in the infertility market, 2005-06 81

Figure 16: Organon’s 7MM infertility franchise by brand, 2006 84

Figure 17: Merck Serono’s 7MM infertility franchise by brand, 2006 87

Figure 18: Ferring’s seven major market infertility franchise by brand, 2006 89

Figure 19: SWOT analysis of the infertility market across the seven major markets, 2007 92

Figure 20: Mother’s age at first birth in France, Germany, Spain and Italy, 1985-2000 93

Figure 21: Ferring’s fertility website 98

Figure 22: Breakdown of fertility market pipeline by development status, 2007 106

Figure 23: Datamonitor’s comparative forecast of sales for the follitropins across the IMS-derived, seven major markets ($m), 2007-2016 117

Figure 24: Datamonitor’s competitive positioning analysis for Puregon and Org-36286 in the IMS derived, seven major markets, 2007-2016 119

Figure 25: Historical sales for the follitropins, Puregon and Gonal-F, 2003-06 124

Figure 26: Datamonitor’s competitive positioning analysis for Org-36286 in the IMS-derived, seven major markets, 2007-2016 126

Figure 27: Datamonitor’s forecast of sales for Org-36286 across the seven major markets ($m), 2007-2016 127

Figure 28: Datamonitor’s comparative forecast of sales for the menotropins across the IMS-derived, seven major markets ($m), 2007-2016 134

Figure 29: Datamonitor’s competitive positioning analysis for Menopur and Pergoveris in the IMS-derived, seven major markets, 2007-2016 136

Figure 30: Historical sales for the top three menotropins Menopur, Menogon and Humegon, 2003-06 139

Figure 31: Datamonitor’s competitive positioning analysis for Pergoveris in the IMS derived, seven major markets, 2007-2016 141

Figure 32: Datamonitor’s forecast of sales for Pergoveris across the IMS derived, seven major markets ($m), 2007-2016 142

Figure 33: Market share and growth of the E7 infertility markets, 2005-06 152

Figure 34: Reproductive migration of Italian couples in 2003 and 2005 158