The cost of treating rare disease in an age when austerity measures are hitting total healthcare funding across Europe is a highly controversial, even emotive subject. There is a clear and pressing clinical need, a strong patient voice and the treatments themselves sometimes offer the only hope. But is this enough to assure premium prices and special status in an era of budget limitations, and growing demands for evidence of clinical and cost effectiveness?

The orphan drug Regulation 141/2000, resulting in 724 designated products and 62 marketing approvals in the first 10 years, has certainly been one of the most successful legislative measures by the EU. Encouraging development and accelerating regulatory approval are very important, but alone do not ensure orphan drugs are actually available for use. Rare disease patients need timely access to therapies that are fully funded by social health insurance/national health services. Hurdles are found at national, regional and local level. Discover what these are and the strategies employed by successful orphan drug companies.

Orphan Drugs in Europe: Pricing, Reimbursement, Funding & Market Access, 2011 Edition is a fully revised and greatly enlarged version of the best-selling 2008 report, and the author’s fifth major title on orphan drugs.

Updated to May 2011, it includes:

- Availability, price and reimbursement status for all 60 EU-designated orphan drugs with centralised marketing authorisations up to end-2010.
- How orphan drug policies differ across Europe. Expanded sections on each EU-5 country. Situation in 20 countries described in total.
- Key role of special ‘high cost’ funding systems explained.
- Impact of health technology assessment.
- The myths and realities of orphan drug costs.
- How risk sharing schemes and patient registries can help bridge the data gap.
- Ways to provide pre-approval early access.
- 12 case studies.
- The potential for EU collaboration on clinical added value of orphan drugs.

Executive Summary

1. EU rphan Drug Regulatin
1.1 bjectives
1.2 Qualifying Criteria
1.3 Prcedure/Timetable
1.4 Incentives
1.4.1 Prtcl Assistance
1.4.2 Marketing Apprval Assistance
1.4.2.1 Pririty review/fast track assessment
1.4.2.2 Lwer regulatry fees
1.4.3 Marketing Exclusivity
1.4.3.1 Issues relating t similarity
1.5 rphan Designatin Withdrawn
1.6 Exclusivity Withdrawn
1.7 Cmparisn with US and ther rphan Drug Plicies
1.8 Results
1.8.1 Designatin
1.8.2 Marketing Apprval
1.9 Paediatric Regulatin
1.9.1 Paediatric rphan Drugs

2. Cncerns Raised by Payers
2.1 ‘There are s many rare diseases’
2.2 ‘A tidal wave f new rphan drugs is cming’
2.3 ‘Funding needs are ften life lng’
2.4 ‘Clinical data are very limited’
2.4.1 Questins n efficacy
2.4.2 Questins n dsage
2.4.3 Questins n safety
2.5 ‘Patient numbers are uncertain’
2.6 ‘Prices are arbitrary and t high’
2.7 ‘Market exclusivity stifles cmpetitin’
2.8 ‘rphan drugs are nt cst effective’
2.9 ‘Funds are diverted frm treating mre cmmn cnditins’
2.10 ‘Anther rphan indicatin sn fllws the first’
2.11 ‘Industry pursues a lw-risk rare disease strategy’
2.12 ‘rphan drugs may turn int blckbusters’
2.13 ‘Increased interest in rphan develpment by Big Pharma’
2.14 ‘Expensive prducts replace cheaper alternatives’

3. Respnse by Industry and Patient Advcacy Grups
3.1 N Excessive Pricing
3.2 N Saring Csts
3.3 N Market Mnply
3.4 N Fld f New rphan Drugs
3.5 N Lack f Clinical Trials
3.6 Risk Sharing Schemes
3.6.1 Italy
3.6.2 UK
3.7 N Particular Safety Issues
3.8 Registries Prvide Pst-marketing Evidence
3.9 Public Supprt fr rphan Drug Funding

4. Market Access
4.1 Early Access Schemes
4.2 Cmmercial Distributin
4.3 rphan Drug Availability
4.4 rphan Drug Prices
4.5 Eurrdis 2010 Survey
4.6 rphan Drug Utilisatin

5. Situatin in EU-5
5.1 France
5.1.1 Cmpassinate Use
5.1.2 Pricing & Reimbursement
5.1.3 Health Ecnmic Cnsideratins
5.1.4 Hspital Funding
5.1.5 Incentives fr rphan Drugs
5.1.6 P&R Results with rphan Drugs
5.1.7 Market Access Situatin
5.1.8 Rare Disease Patient Grups
5.2 Germany
5.2.1 Cmpassinate Use
5.2.2 Pricing & Reimbursement
5.2.3 Health Ecnmic Cnsideratins
5.2.4 Hspital Funding
5.2.5 Incentives fr rphan Drugs
5.2.6 P&R Results with rphan Drugs
5.2.7 Market Access Situatin
5.2.8 Rare Disease Patient Grups
5.3 Italy
5.3.1 Cmpassinate Use
5.3.2 Pricing & Reimbursement
5.3.3 Health Ecnmic Cnsideratins
5.3.4 Incentives fr rphan Drugs
5.3.5 Market Access Situatin
5.3.6 Rare Disease Patient Grups
5.4 Spain
5.4.1 Cmpassinate Use
5.4.2 Pricing & Reimbursement
5.4.3 Health Ecnmic Cnsideratins
5.4.4 Hspital Funding
5.4.5 Incentives fr rphan Drugs
5.4.6 Market Access Situatin
5.4.7 Rare Disease Patient Grups
5.5 United Kingdm
5.5.1 Cmpassinate Use
5.5.2 Pricing & Reimbursement
5.5.3 Health Ecnmic Cnsideratins
5.5.3.1 NICE
5.5.3.2 SMC
5.5.3.3 AWMSG
5.5.3.4 Nrthern Ireland
5.5.3.5 utcme
5.5.4 Hspital Funding
5.5.4.1 High cst PbR exclusins
5.5.4.2 Pass thrugh payments
5.5.4.3 Specialist cmmissining
5.5.5 Incentives fr rphan Drugs
5.5.6 Market Access Situatin
5.5.7 Rare Disease Patient Grups

6. Situatin in ther Eurpean Cuntries
6.1 Austria
6.2 Belgium
6.2.1 Pricing & Reimbursement
6.2.2 rphan Incentives
6.2.3 Special Funding Prvisins
6.2.4 Market Access Situatin
6.3 Bulgaria
6.3.1 Special Funding Prvisins
6.3.2. Market Access Situatin
6.4 Cratia
6.5 Czech Republic
6.5.1 Pricing & Reimbursement
6.5.2 Market Access Situatin
6.6 Denmark
6.7 Greece
6.7.1 rphan Incentives
6.7.2 Special Funding Prvisins
6.8 Hungary
6.9 Ireland
6.10 Netherlands
6.10.1 Pricing & Reimbursement
6.10.2 rphan Incentives
6.10.3 Special Funding Prvisins
6.10.4 Market Access Situatin
6.10.5 Prpsals fr Change
6.11 Pland
6.11.1 Pricing & Reimbursement
6.11.2 Special Funding Prvisins
6.11.3 Market Access Situatin
6.12 Rmania
6.13 Russia
6.14 Sweden
6.14.1 Pricing & Reimbursement
6.14.2 Hspital Funding
6.15 Switzerland

7. EU Initiatives
7.1 Cmmunity Actin Prgrammes
7.2 rphanet
7.3 Pharmaceutical Frum
7.4 Cmmunity Framewrk Prgrammes
7.5 EU Cmmittee f Experts n Rare Diseases
7.6 Natinal Plans
7.7 Cllabrative Effrts t Imprve rphan Drug Access
7.8 Directive n Crss-brder Healthcare

8. Cnclusins

Case Studies
C-exclusivity fr agalsidases in Fabry disease
C1 esterase inhibitrs fr hereditary angiedema: what is unique?
Withdrawal f Thelin
Eurpe’s mst expensive rphan drug
Is a price premium fr cmmercial amifampridine justified?
Filling the vid in Gaucher Therapy
Patient access schemes with Velcade
Named patient distributin f Ceplene
Secnd generatin tyrsine kinase inhibitrs fr CML
Re-evaluatin f PAH treatments in France
Varying HTA results fr Myzyme in UK
Evidence develpment agreement with Dudpa in Sweden

Tables
1.1 verview f EU rphan drug prcedure, 2000-10
1.2 Distributin f psitive CMP decisins by therapeutic area
1.3 Marketing authrisatins fr rphan designated medicines, 2000-10
1.4 Apprved treatments fr main lyssmal strage disrders
1.5 Distributin f rphan MAs by therapeutic area, 2000-10
1.6 rphan drugs with marketing apprval, by INN
1.7 rphan drugs with marketing apprval, by brand name
2.1 Size f pre-marketing clinical trials with apprved rphan drugs
2.2 Rare diseases with the mst rphan drug apprvals in US
2.3 Previusly available therapeutic alternatives fr rphan drugs
3.1 Examples f risk-sharing agreements with rphan drugs
3.2 Number f rare disease registries by cuntry
4.1 Sme cmparisns f CEE cuntries with Germany
4.2 Strategic cnsideratins in charging fr pre-apprval sales
4.3 Principal distributin channels fr rphan drugs
4.4 EU-5 availability f reimbursed rphan drugs by cuntry
4.5 Public prices f rphan drugs in EU-5
4.6 Maximum MSPs f selected rphan drugs by cuntry
4.7 Eurrdis 2010 survey f rphan drugs by cuntry
4.8 N. patients with access t rphan drugs by therapeutic area
5.1 ASMR scres fr rphan drugs in France
5.2 Reimbursement status f rphan drugs in France
5.3 rphan drugs n ZE and NUB lists fr hspital payment in Germany
5.4 ZE rates by dsage fr Glivec in Germany
5.5 rphan drugs nt recmmended fr NHS in devlved parts f UK
5.6 High cst rphan drug exclusins frm PbR in England
6.1 Reimbursable rphan drugs in Belgium
6.2 rphan drugs reimbursed in Bulgaria
6.3 Maximum MSPs and reimbursement limits fr rphan drugs in Czech Republic
6.4 Intramural and extramural rphan drugs reimbursed in Netherlands
6.5 rphan drugs reimbursed under therapeutic prgrammes in Pland
6.6 Cverage by ‘seven nslgies’ prgramme in Russia
6.7 Swedish cst effectiveness estimates fr reimbursed rphan drugs
7.1 Rare diseases with highest numbers f clinical trials in Eurpe

Appendices
1. Examples f rphan medicines predating the EU Regulatin
2. EU designated rphan drugs with centralised marketing authrisatins
3. Crss-natinal cmparisn f rphan drug plicies

Glssary f Abbreviatins and Acrnyms
Surces used fr Prduct Availability & Price Infrmatin
References