EUROPEAN HAEMOPHILIA CONSORTIUM Supporting R&D in Rare Diseases: Barriers and Incentives

1. www.eurordis.org EUROPEAN HAEMOPHILIA CONSORTIUM Supporting R&D in Rare Diseases: Barriers and Incentives Brussels, 7 December 2011

2. EU REGULATION ON ORPHAN DRUGS: 11 YEARS ON WHAT CHALLENGES REMAIN FOR THE PATIENTS Yann LE CAM Yann Le Cam Chief Executive Officer EURORDIS Vice-Chair of EU Committee of Experts on Rare Diseases Brussels 7 December 2011

3. 2000 – 2011: Consolidating EU Regulatory Environment • EU Regulation on Orphan Medicinal Products • Adopted in 1999, implemented since 2000 • Creation of the Committee for Orphan Medicinal Products at the European Medicines Agency (including 3 patients’ representatives for the first time) • Commission Communication on Orphan Medicinal Products, 2003 • EU Regulation on Paediatric Use Medicines • Adopted in 2006, implemented since 2008 • Creation of the Committee for Paediatric Drugs at the European Medicines Agency (including 3 patients’ representatives and their alternates) • EU Regulation on Advanced Therapies • Adopted in 2007, implemented since 2009 • Creation of the Committee for Advanced Therapies at the European Medicines Agency (including 2 patients’ representatives and their alternates)

4. Incentives provided by the EU Orphan Drug Regulation (141/2000 ) • Main incentives: • Market exclusivity for a period of 10 years after EU marketing autorisation • 2 years extension of market exclusivity for orphan drugs for children (overall 12 years) • Other incentives: • Fee reductions: Orphan designation 100%, Protocol assistance • (SMEs 100%, Non-SMEs 75%), Marketing authorisation application (SMEs 100%, Non-SMEs 10%) • Protocol assistance • Priority to EU Research - Framework programmes • Access to Member States Incentives

5. Overview of Orphan Medicinal ProductDesignation and Marketing Authorisation • Designations as per COMP report at September 2011 • Marketing Authorisations s as per COMP report at September 2011 • (http://ec.europa.eu/health/documents/community-register/html/orphreg.htm) • 72 Orphan Products with MA in September 2011 (61 different products)

6. CHALLENGES The EU Regulation on Orphan Drugs has proven to be successful to enhance research in rare diseases and bring new therapies to the market. However, improvements need to be made: • Unmet medical needs: Some disease areas are neglected, • 1/3 of Orphan Drugs Designation (ODD) in oncologic area * • (For certain diseases, there is a large number of ODD (e.g. 33 ODD for the cystic fibrosis indication, 37 for glioma), but only 1 marketed drug. Why such a disproportion? * * = source COMP

7. CHALLENGES • Where are our future higher risks? • Reimbursement & Healthcare Budgets’ Constraints? • Reimbursement based on generated data or value based • Better targeting of patients & better medical practices • Revision of EU Directive on Clinical Trials & Directive on Data Protection • Rapidly changing landscape on off-label?

8. Vision and Action: Innovative Approaches to Access to Orphan Products •  Coordinated approach at EU level • CAVOD: a process to generate better data at time of MA and for post-MA research activities to assess the Clinical Added Value of Orphan Drugs (real life value, not clinical trial value) and the actual place of the product within the therapeutic strategy of the disease • MOCA:Mechanism of Coordinated Access to Orphan Drugs between Member States, based on value, volume, access, generation of knowledge

9. Vision and Action: CAVOD MECHANISM SignificantBenefit, COMP EC marketing authorisation T0 + 90 days T0+ΔT (after 3 to 5 years, flexible depending of the disease) CHMP opinion, T0 Period 2: for simple Compilation report & evidence generation plan Period 4: relative effectiveness assessment Period 1: for EMA / EUnetHTA coordination Period 3:for follow up of the evidence generation plan Time Source: Ernst & Young; Executive Agency for Health & Consumers

10. VISION AND ACTION: New Paradigmes • Focus on Effectiveness beyond Quality, Safety, Efficacy Adapt Clinical Trial designs, as early as possible Adapt Post MA Research plan • Better and broader collection of relevant data Data collected all along the life cycle of the medicine on risks as well as on benefits: compassionate use, real life studies (actual heterogeneous population and real life constraints beyond clinical trials), off label use Development of harmonised patient registries

11. VISION AND ACTION: New Paradigmes • Regulatory flexibility and supportive approach: A roll-over process beyond MA, before and after MA Progressive approval EMA – FDA stronger collaboration e.g. Protocol assistance, MA, post-MA research

12. VISION AND ACTION: New Paradigmes • Early dialogue between health authorities and industry Priority to unmet medical needs Pre-marketing agreements • Fairness and transparency in cost construction and pricing for long term sustainability • Promotion of RDs as an international public health priority • Link to essential societal values and refine what is value of orphan drugs

13. UPCOMING POLICY EXPERT GUIDANCE with an international perspective • EUCERD Recommendation on Quality Criteria for Centres of Expertise on Rare Diseases • EUCERD Recommendation on Quality Criteria for European Reference Networks on Rare Diseases • EUCERD Recommendation on Clinical Added Value of Orphan Drugs (CAVOD) • EUCERD Recommendation on Patient Registries • EUCERD Recommendations on Quality Testing • EUCERD Recommendation on Population Screening

14. Current Priorities in EU Policy Environment with an International Perspective • EU Directive Cross-Border Healthcare– 9 March, 2011 • Rare Diseases: is reiterated as a top priority • Legal base European Reference Networks for Rare Diseases • Mobility of patients across EU • Strengthen EU cooperation on HTA => All these points have direct impact on Access • 2nd & 3rd EU Public HealthProgramme (2014 – 2020) • 7th & 8th EU Research & Technology Framework Programme (2014 – 2020)

15. GROWINGLY STRUCTURED NETWORKS with an international perspective • EURORDIS (1997) & Strategic Partnership with NORD • ORPHANET (1998) • IRDiRC: International Rare Diseases Research Consortium (2011) • Clinical Research Networks (e.g. ECRIN 2006) • Common Infrastructures on Biobanks (2001), Registries and databases (2012-2018) • Common Methodologies on Good Clinical Practices (2012-2014) • European Reference Networks for Rare Diseases (pilots since 2008, expansion from 2014)? • Collaboration EMA & FDA beyond designation (2008)? • EMA dialogue with HTA & Payers + Patients & Experts (2010)? • EUnetHTA (2009) + Core common methodology (2011) + CAVOD (2012)? • EFPIA & PHARMA & IFPMA?

16. THANK YOU !