ABOUT DATAMONITOR HEALTHCARE 2
About the Strategic Pharmaceutical Analysis Team 2
Executive Summary 3
Strategic scoping and focus 3
Datamonitor insight into the disease market 3
Related reports 5
Table of Contents 6
2. Orphan drug overview 7
Key findings 7
Orphan drug definitions 8
US orphan drug criteria 9
EU orphan drug criteria 9
Japanese orphan drug criteria 10
Orphan drug designation comparisons across the US, EU, and Japan 11
Ultra-orphan drug and disease criteria 12
Drivers and resistors to orphan drug development and commercialization 13
Developmental and commercial barriers to orphan drugs 13
The rate of uptake of orphan drugs is similar to that of non-orphan drugs 14
Orphan drug status offers no protection against generic erosion 17
Drivers and incentives for orphan drug development and commercialization 18
Market-specific orphan drug incentives 20
US incentives 20
EU initiatives 22
Japanese initiatives 24
3. Orphan drug development and approval trends 26
Key findings 26
Orphan drug designation and approval trends 27
Decline in recent number of US orphan drug designations linked to Biotech funding crisis 27
2009 decline in orphan drug designations linked to biotech funding crisis 29
Continued forecast growth for European orphan drug designations and approvals 30
Factors contributing to EMEA refusal of orphan drug designations 32
Orphan drug approval trends in Japan 34
Orphan drug research and development trends 35
Clinical trial and approval strategies for orphan drugs 35
Adaptive clinical trials ideally suited to orphan drug assessment 38
Orphan drug pipeline trends 40
Orphan drug reimbursement issues 45
Orphan drug access in the US 45
Orphan drug access in Europe 45
Orphan drug risk-sharing in the UK set to become more frequent driven by new drug launches and disease stratification 46
4. Orphan drug strategies and future outlook 48
Key findings 48
Big Pharma's growing attraction for orphan drugs 49
Big Pharma's dominance in the orphan drug market 50
Strategies employed to grow Big Pharma's orphan drug presence 51
Three key orphan drug strategies 52
Market access and subsequent expansion into non-orphan diseases offers significant opportunity for revenue generation 53
Multiple indications shore up a drug's exclusivity in a niche therapeutic area 53
Stratification of indications into niche patient populations 55
Segmentation through pediatric orphan indications and disease specialization 56
The growing use of biomarkers in disease stratification 56
Orphan drug specialists 58
Genzyme's success in ultra-orphan markets 58
Actelion's orphan drug portfolio driven by pulmonary arterial hypertension 59
Orphan drug sales forecast 61
5. Bibliography 63
Publications and online articles 63
Datamonitor reports 69
APPENDIX 70
About Datamonitor 73
About Datamonitor Healthcare 73
Datamonitor consulting 73
Disclaimer 75
List of Tables
Table 1: Comparison of orphan product policies across the US, EU and Japan, 2009 11
Table 2: Non-orphan, orphan and ultra-orphan drug designations in the US, 2009 12
Table 3: Comparison of orphan and non-orphan drug growth rates after launch, 2005-08 14
Table 4: Comparison of access to orphan drugs in selected EU countries, 2009 23
Table 5: Summary of US and EU orphan drug designations, approvals and approval rates, 1980s-2000s 28
Table 6: Top 20 most frequently targeted orphan indications by manufacturers in the EU, 2000-08 43
Table 7: FDA approved orphan drugs with multiple indications, 2009 54
Table 8: Drugs with at least one orphan drug status and associated orphan biomarkers 57
Table 9: Most frequently targeted orphan indications by manufacturers in the EU, 2000-08 70
Table 10: Exchange rates, 2008 72
List of Figures
Figure 1: Orphan drug policies by country 8
Figure 2: Uptake of orphan and non-orphan drugs during the first 3 years post launch, 2005-08 15
Figure 3: Erosion of orphan drugs versus average US brand erosion following patent expiry, 2005-08 17
Figure 4: The sliding scale of blockbuster sales: primary care drugs to ultra-orphan drugs 18
Figure 5: Factors driving the shift away from the primary care blockbuster model towards niche indications 19
Figure 6: Molecule type of approved orphan drugs, 2007 27
Figure 7: Number of designated and approved orphan drugs in the US, 1993-Q2 2009 29
Figure 8: Number of designated, approved, withdrawn/suspended and refused orphan drugs in the EU, 2000-Q2 2009 30
Figure 9: Number of orphan drug designations across a selection of European countries, 2000-07 31
Figure 10: Factors responsible for refusal of EMEA market authorization 32
Figure 11: Factors responsible for refusal of EMEA orphan drug designations 33
Figure 12: Number of orphan drugs receiving approval from the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), 2004-07 34
Figure 13: US orphan drug Phase I-III clinical trial designs, 2009 36
Figure 14: Orphan drug comparator designs by phase of clinical trial 37
Figure 15: Reasons for adopting adaptive clinical trials for orphan drugs 38
Figure 16: Factors to be considered when designing an adaptive clinical trial 39
Figure 17: US and European pipeline orphan designated drugs by clinical trial phase, 2009 40
Figure 18: US pipeline orphan designated drugs by therapy area, 2009 41
Figure 19: EU orphan drug market authorizations by therapy area, 2008 42
Figure 20: Japanese orphan drug approvals by therapy area, 2004-07 44
Figure 21: Factors to consider when developing risk-sharing agreements for orphan drugs 47
Figure 22: End goals of orphan drug strategies for biotech and Big Pharma 49
Figure 23: Orphan drug developers split by company type, 1990-2008 50
Figure 24: Orphan drug strategies to increase revenue potential through sales expansion or protection 52
Figure 25: Criteria to be considered when stratifying a disease into smaller niche and potentially orphan indications 55
Figure 26: Forecast global sales of Genzyme's orphan and non-orphan drug portfolios, 2008-2014 59
Figure 27: Forecast global sales of Actelion's orphan and non-orphan drug portfolios, 2008-2014 60
Figure 28: Historical and forecast sales of drugs with orphan status for at least one indication, marketed by the top 50 global pharmaceutical companies in the US and five major EU market, 2001-2014 62