Overview 1
Catalyst 1
Summary 1
About Datamonitor Healthcare 2
About the cardiovascular and metabolic analysis team 2
Executive Summary 3
Scope of the analysis 3
Datamonitor insight into the hemophilia market 3
Related reports 4
Table of Contents 5
Chapter 1 Patient Potential 6
Definition 7
Classification 8
Grading 13
Screening, diagnosis and monitoring 14
Sequelae, complications and unintended consequences 17
Epidemiology 20
Incidence 20
Expected versus reported prevalence 22
Capture by severity 25
Age distribution 28
Chronic viral infection rates 31
Human immunodeficiency virus 33
Hepatitis C 35
Inhibitors 38
Chapter 2 Current treatment 42
Currently available treatments 42
Factor-replacement therapies 42
Adjunct and bypassing therapies 46
Treatment strategies 46
Prophylactic treatment 49
The ideal: earlier primary prophylaxis through comprehensive care 49
The challenge: an unsustainable cost versus broader healthcare priorities? 54
On-demand treatment 58
In response to a bleed 58
Surgery and dentistry 60
Inhibitors 62
As an alternative to prophylaxis 66
Seven major market treatment trends 67
Chapter 3 Unmet need 74
Access to therapeutics 74
Developed economies 74
Developing economies 76
Curative therapy 77
Tackling the inhibitor conundrum 82
Convenience and quality of life 83
The human immunodeficiency virus and hepatitis legacy 84
Chapter 4 Future directions 85
Protein engineering 85
Conjugation 85
Fusion proteins 86
Hybrid proteins 86
Other factor variants 87
Other approaches: delivery vehicles, gene therapy, small molecule therapeutics and others 88
Bibliography 89
Journals 89
Books 95
Websites 95
Datamonitor reports 96
Appendix A 97
Treatment protocols 97
Appendix B 101
Acknowledgements 101
Report methodology 101
About Datamonitor 102
About Datamonitor Healthcare 102
About the cardiovascular and metabolic analysis team 103
Disclaimer 105
List of Tables
Table 1: Categorization and common causes of excessive bleeding 8
Table 2: Hemophilia, von Willebrand's disease and single-factor deficiencies: causes, inheritance, treatments and idiosyncrasies 10
Table 3: Hemophilia severity categorization: factor activity levels, common bleed types and causes and management approach 13
Table 4: Screening tests for bleeding disorders 15
Table 5: Worldwide hemophilia A and B birth prevalence, the US, Japan, the five major EU markets (5EU) and the rest of the world, 2009 est. 22
Table 6: Worldwide expected hemophilia prevalence by severity, US, Japan, the five major European markets (5EU) and the rest of the world, 2009 26
Table 7: Worldwide reported hemophilia prevalence by severity: the US, Japan, the five major European markets (5EU) and the rest of the world, 2009 28
Table 8: Distribution of hemophilia population by age, hemophilia A, hemophilia B and totals for the US, Japan and the five major European markets (%) 31
Table 9: Number and proportion of reported hemophilia A and B cases with clinically identified inhibitors 39
Table 10: Expected inhibitor patient numbers, expected inhibitor prevalence rates and relative capture versus reported inhibitor patient numbers in the seven major markets 40
Table 11: Definitions of replacement treatment regimens in hemophilia 47
Table 12: High- and intermediate-dosing regimens for hemophilia A and B versus select product labeling 50
Table 13: Typical amount of factor VIII required per year to treat an adult with severe hemophilia in IUs 54
Table 14: Cost of care: factor VIII versus etanercept and blood glucose test strips in Sweden 57
Table 15: Mean and median numbers of joint-specific and total hemorrhages per patient per year, prophylaxis versus enhanced episodic therapy in boys with severe hemophilia 59
Table 16: Summary of inhibitor management strategies, tactics, advantages and disadvantages 63
Table 17: World Federation of Hemophilia, desired plasma factor level and dosage for bolus infusions, 2008 97
Table 18: Changes in World Federation of Hemophilia hemorrhage treatment protocols between 2006 and 2008, implications, and previously recommended treatment duration 98
List of Figures
Figure 1: The clotting cascade, key factors and diagnostic test sites 7
Figure 2: Inheritance patterns for hemophilia A and B 12
Figure 3: Hemophilia screening, diagnosis and monitoring: processes and methodologies 14
Figure 4: Rationale for genetic testing for hemophilia 16
Figure 5: Hemophilia: sequelae, complications and consequences 17
Figure 6: Deaths among persons with hemophilia A for those with and without disease related to human immunodeficiency virus, and overall age-adjusted death rate, by year, the US, 1979-1998 19
Figure 7: Worldwide hemophilia A and B birth prevalence and share, seven major markets and rest of world, 2009 est. 21
Figure 8: Worldwide birth, expected and reported prevalence and prevalence share, US, Japan, five major European markets and rest of world, 2009 24
Figure 9: Worldwide reported hemophilia prevalence by severity as a percentage of expected prevalence: the US, Japan, the five major European markets and the rest of the world, 2009 27
Figure 10: Distribution of total reported hemophilia A and B populations by age for the US, Japan, France, Germany, Italy, Spain and the UK (%) 30
Figure 11: Current hepatitis C and human immunodeficiency virus prevalence among hemophilia and general populations in the US, Japan, France, Germany, Italy, Spain and the UK 32
Figure 12: Hemophilia deaths in Germany by cause (human immunodeficiency virus, liver disease and malignancy), 1982-2008 33
Figure 13: Relative prevalence of human immunodeficiency virus: general population versus reported hemophiliacs 34
Figure 14: Relative prevalence of hepatitis C: general population versus reported hemophiliacs 37
Figure 15: Proportional rates of infection with human immunodeficiency or hepatitis C infection 38
Figure 16: Projected distribution of monthly care burden for reported hemophilia patients with inhibitors, seven major markets 41
Figure 17: Key characteristics of factor-replacement products: specificity, source material, safety, purification and content 43
Figure 18: Blood components 44
Figure 19: Relative public health service pricing costs of recombinant factor VIII products, 2001-04 46
Figure 20: 100 years of hemophilia 48
Figure 21: Drivers and resistors for primary prophylaxis 49
Figure 22: Relative stakeholder benefits of comprehensive care in hemophilia 51
Figure 23: Benefits of comprehensive care in hemophilia 52
Figure 24: Hemophilia-specific facilities available at centers of expertise 53
Figure 25: Primary prophylaxis, continuous secondary prophylaxis, periodical secondary prophylaxis and on-demand therapy in 22 European centers, 2003 55
Figure 26: US distribution of patients by treatment approach and factor usage, 1996-98 56
Figure 27: Drivers and resistors for the supply and demand of surgery in hemophilia 61
Figure 28: Approaches to managing inhibitors in hemophilia 62
Figure 29: Treatment decision tree for first-line therapy in inhibitor patients, Germany 64
Figure 30: Alternative treatment options for developing economies 67
Figure 31: Reported use of recombinant versus plasma products in the US, Japan, France, Germany, Italy, Spain and the UK 68
Figure 32: Factor usage per reported hemophilia case in the US, Japan, France, Germany, Italy, Spain and the UK 69
Figure 33: Proportional reported use of recombinant versus plasma products in the US, Japan, France, Germany, Italy, Spain and the UK 70
Figure 34: Reported per capita factor VIII and factor XI usage across hemophilia A and hemophilia B patients in the US, Japan, France, Germany, Italy, Spain and the UK 71
Figure 35: Factor VIII and factor IX volume usage potential through hemophilia A and hemophilia B per capita usage and identified population increase in the US, Japan, France, Germany, Italy, Spain and the UK 73
Figure 36: Monogenic genetic disorders: life expectancy with and without standards of care versus live birth prevalence 80
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