Stakeholder Opinions: Pulmonary Arterial Hypertension clinical community builds order from chaos

Despite an explosion in the number of drugs and treatment strategies available, pulmonary arterial hypertension is still a rapidly fatal condition for a small, hard to identify patient group. A small clinical elite is currently leading the way in advancing treatment outcomes, and is central to determining which new treatment strategies are used.

Report Highlights
The estimated 8,11516,186 diagnosed pulmonary arterial hypertension patients across the US, Japan, France, Germany, Italy, Spain and the UK represent a fraction of the 28.0135.6 million group known to be at elevated risk. Identifying the true patient potential within known high risk groups remains highly problematic.

A small, but relatively powerful clinical community has brought structure, order and an increasing influence to bear on management through a few specialist centers. This internationally cohesive group has been responsible for laying the foundations for substantial volumes of data pertaining to patients managed in increasingly standardized ways.

A high number of approved and late stage pipeline products, and the increasing exploration of combination therapeutics places a higher emphasis than normal on the perceptions of specialist clinicians, who will increasingly need to triage their attentions to the most promising avenues for improving outcomes.
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ABOUT DATAMONITOR HEALTHCARE 2
About the cardiovascular analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Strategic scoping and focus 3
Datamonitor insight into the disease market 3
Related current reports 5
Related future reports 5
CHAPTER 2 MARKET DEFINITION 7
Market definition for this report 7
Geographic coverage 7
Defining pulmonary arterial hypertension 7
CHAPTER 3 DISEASE BACKGROUND 9
The short and animated history of pulmonary arterial hypertension 9
Aminorex flags a problem 12
WHO symposium drives hunt for definitions 12
National Institutes of Health registry sets the standard 12
Evian creates structure, IPPHS and SNAP offer etiological insight 12
Venice improves standardization, maps future directions 13
Dana Point: consensus and contention 16
Classification - largely unchanged but ""pre-PAH"" pondered 16
Genetics still too nebulous, but prognostic and risk factors at the fore 17
Exponential rise in commercial interest 18
Modest beginnings 19
The drug development surge 20
PAH-specific treatments 24
Marketed drug summaries 31
Endothelin receptor antagonists 31
Prostacyclin agonists 34
Phosphodiesterase-5 inhibitors 38
CHAPTER 4 THE CURRENT CLINICAL PARADIGM 39
Introduction 39
Earlier diagnosis: 39
The clinical community: 39
The broader patient potential: 40
A diagnosis of exclusion 40
Lengthy, costly, risky diagnoses of exclusion: ideal for missing cases? 40
Few immediate prospects for improved diagnostic capabilities 43
Experimentation, documentation, standardization 44
The importance of the clinician power-base 44
The evolution of consensus 49
Compare and contrast: European and US guidelines 50
Expanding patient population or expanding at-risk population? 56
A miniscule patient group diagnosed too late? 56
Pre-PAH: increasing the identified ""at-risk population""? 59
CHAPTER 5 DEMANDS OF THE FUTURE PARADIGM 64
Improved outcomes - with data or without it 65
EU and US guideline convergence? 68
Clear guidance on product positioning essential 70
Balancing pressure on trial design against reasonable expectation 77
New approaches and treatments 81
Triage and selectivity are the watchwords 81
The commercial expectation 84
Pipeline overview 88
BIBLIOGRAPHY 95
Journal papers 95
Presentations 104
Website information 104
Books 107
Datamonitor reports 107
APPENDIX A - EPIDEMIOLOGICAL ASSUMPTIONS 108
Total population data 111
Incidence and prevalence 112
Incidence 113
Prevalence 114
Functional class at time of diagnosis 114
Etiology and functional class/etiology 116
Gender and gender/etiology 121
Patient potential 125
Note on data limitations 129
APPENDIX B 131
Contributing experts 131
Report methodology 131
About Datamonitor 132
About Datamonitor Healthcare 132
About the Cardiovascular Disease analysis team 133
Disclaimer 134
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Table 1: Clinical classifications of pulmonary arterial hypertension - Venice, 2003 15
Table 2: New York Heart Association/World Health Organisation classification of functional status of patients with pulmonary arterial hypertension 16
Table 3: Overview of marketed products for pulmonary arterial hypertension, 2009 20
Table 4: Drug development activity and active approvals per year - pulmonary arterial hypertension versus select breakthrough indications, in the seven major markets 24
Table 5: Currently approved therapies for pulmonary arterial hypertension - class, formulation, dosing, reimbursement and primary and secondary indications, 2009 28
Table 6: Letairis (ambrisentan) overview 31
Table 7: Tracleer (bosentan) overview 32
Table 8: Thelin (sitaxsentan) overview 33
Table 9: Flolan (epoprostenol) overview 34
Table 10: Careload LA (beraprost) overview 35
Table 11: Ventavis (iloprost) 36
Table 12: Remodulin (treprostinil) overview 37
Table 13: Revatio (sildenafil) overview 38
Table 14: Comparative American College of Chest Physicians' (ACCP) and European Society of Cardiology (ESC) clinical guidance coverage for pulmonary arterial hypertension 51
Table 15: UK interim national commissioning policy for pulmonary arterial hypertension management, 2008 55
Table 16: Pulmonary arterial hypertension therapy involvement in combination trials - as backbone, add-on or combination component 70
Table 17: Overview of pulmonary arterial hypertension combination and add-on trial 73
Table 18: Phase III pipeline overview for pulmonary arterial hypertension, 2009 89
Table 19: Phase II pipeline overview for pulmonary arterial hypertension, 2009 90
Table 20: Phase I and selected preclinical pipeline overview for pulmonary arterial hypertension, 2009 92
Table 21: Seven major market population data, 2009 111
Table 22: Estimated incidence and prevalence rates of pulmonary arterial hypertension in the 5EU, US and Japan, 2008 112
Table 23: Estimated incidence and prevalence of pulmonary arterial hypertension, in the 5EU, US and Japan, 2008 112
Table 24: New York Heart Association classification of pulmonary arterial hypertension patients at time of presentation by functional class in the seven major markets, 2009 114
Table 25: Functional class at presentation - high and low pulmonary arterial hypertension incidence and prevalence rates for the seven major markets 115
Table 26: Etiology at the time of diagnosis of pulmonary arterial hypertension for the seven major markets 116
Table 27: Etiology at the time of diagnosis of pulmonary arterial hypertension - incidence and prevalence ranges in the seven major market 117
Table 28: Etiology and group functional class at the time of diagnosis of pulmonary arterial hypertension in the seven major markets 118
Table 29: Estimated incidence range by etiology and group functional class at the time of diagnosis of pulmonary arterial hypertension in the seven major markets 119
Table 30: Estimated prevalence range by etiology and group functional class at the time of diagnosis of pulmonary arterial hypertension in the seven major markets 120
Table 31: Proportional gender representation by etiology in pulmonary arterial hypertension in the seven major markets 121
Table 32: Estimated proportional gender representation across total incident and prevalent pulmonary arterial hypertension populations in the seven major markets 122
Table 33: Estimates of seven major market incidence of pulmonary arterial hypertension in the seven major markets by etiology and gender, 2008 124
Table 34: Estimates of seven major market prevalence of pulmonary arterial hypertension in the seven major markets by etiology and gender, 2008 125
Table 35: Estimated seven major market epidemiology for conditions associated with pulmonary arterial hypertension 127
Figure 1: Pathophysiology of right ventricular dysfunction in pulmonary hypertension 8
Figure 2: Timeline of key events impacting pulmonary arterial hypertension management, 1950s 2009 11
Figure 3: Determinants of risk in pulmonary arterial hypertension 18
Figure 4: Drug development activity over time - pulmonary arterial hypertension versus select breakthrough indications in the seven major markets 22
Figure 5: Average approvals per year - pulmonary arterial hypertension versus select breakthrough indications in the seven major markets 23
Figure 6: Targets for current therapies in pulmonary arterial hypertension, 2009 25
Figure 7: European Society of Cardiology diagnostic approach for pulmonary arterial hypertension 42
Figure 8: American College of Chest Physicians updated evidence-based clinical practice guidelines for the medical treatment of pulmonary arterial hypertension (2007) 54
Figure 9: Incidence and prevalence ranges for pulmonary arterial hypertension in the US, Japan, and five major EU markets, 2009 57
Figure 10: Seven major market (7MM) incidence and prevalence of pulmonary arterial hypertension by functional class at diagnosis and etiology, 2009 58
Figure 11: New York Heart Association functional class I and II versus III and IV - proportion of patients at diagnosis by etiology 59
Figure 12: Pulmonary arterial hypertension 5-year survival by etiology 61
Figure 13: Estimated incidence and prevalence of populations at risk of pulmonary arterial hypertension in the seven major markets, 2009 63
Figure 14: Improvements in six minute walk test distances, comparison of trial data 66
Figure 15: Relative frequency of product positioning in add-on and combination trials 72
Figure 16: Pipeline overview for pulmonary arterial hypertension, 2009TypeFigTitleHere 88
Figure 17: Pulmonary arterial hypertension epidemiology data integrity and methodology 110
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