1. AIFA European Conference on Clinical Research for Decision Making Which Medicines Do We Need ? Thomas Lönngren, EMEA 30 March 2007

2. Content What are the health trends in EU ? –Demographics –Disease patterns Assessing the needs for medicines –WHO report Priority Medicines for Europe and the world How will decide on the medicines we need ? EMEA role in the need of medicines Conclusion

3. Demographics We are getting older Number of over 80 year olds in EU 15 will increase dramatically over next 15 years Difference between EU 15 and EU 10 Ratio of pensioners to workers will have economic and social consequences Higher cost of health care and medicines is to be expected

4. Demographics

5. Disease patterns Burden of disease –Mental 23%,CVD 17%,Cancer 16.7,Injuries 11%, Respiratory 7.8 Mortality –CVD 42%, Cancer 27%, Injuries 5.2, Mental 4.2% Difference between EU countries –Example Tuberculosis

6. TB Incidence

7. Assessing the needs for medicines WHO report Priority Medicines for Europe and the World Methodology Findings

8. WHO methodology Burden of disease ranking EU10, EU25 The world (including EU25) Cochrane database of systematic reviews Clinical efficacy Projections and trends Social solidarity FINAL REPORT PRELIMINARY LIST OF PRIORITY DISEASES AND GAPS IN DEPTH REVIEWS OF PRELIMINARY LIST OF DISEASES AND GAPS

9. WHO methodology What is the size and nature of the disease burden? What is the control strategy? Why does the disease burden persist? What wan be learnt from past/current research into pharmaceutical interventions for this condition? What is the current “pipeline” of products that are to be used for this particular condition? What are the opportunities for research into new pharmaceutical interventions? What are the gaps between current research and potential research issues which could make a difference, are affordable and could be carried out in a) five years or b) in the longer term? For which of these gaps are there opportunities for pharmaceutical research?

10. Findings on the pharmaceutical gaps 1.Infections due to antibacterial resistance 2.Pandemic influenza 3.Cardiovascular disease (secondary prevention) 4.Diabetes (Type 1 and Type 2) 5.Cancer 6.Acute stroke 7.HIV/AIDS 8.Tuberculosis 9.Neglected diseases 10.Malaria 11.Alzheimer disease 12.Osteoarthritis 13.Chronic obstructive pulmonary disease 14.Alcohol use disorders: alcoholic liver diseases and alcohol dependency 15.Depression in the elderly and adolescents 16.Postpartum haemorrhage

11. Submission of MAA through the Centralised Process are likely to come in phases for key indications Type II Diabetes: novel classes including ‘Gliptins’ and Glucagon-Like Peptide-1 (GLP-1) receptor agonists. Developed as monotherapies and combinations 2010200920082007 Hypertension: multiple submissions per year, third of which could be generic. Large number of combinations Chronic Obstructive Pulmonary Disease/Asthma: multiple novel mechanisms, many as combinations Parkinson’s: possible generics, few novel mechanisms Schizophrenia: compounds targeting combination of Serotinergic and Dopaminergic pathways Insomnia: compounds targeting Serotinergic, GABA and Melatonin pathways Pain: multiple novel mechanisms and generic MAA Rheumatoid arthritis: multiple biological therapies using novel mechanisms Alzheimer’s disease: extensive development including potential disease modifiers Obesity: some development targeting both lipid and CNS pathways Influenza: continued submission of Core Dossier, Pre-pandemic and Seasonal influenza vaccines Oncology: multiple submissions, multiple indications. Increased number of biologicals including therapeutic antibodies, transfected cells, fusion proteins and DNA vaccines

12. Who decides on the medicines we need? Policy makers, EU institutions and individual governments Research-based pharmaceutical industry Regulatory agencies for market approval Pricing and reimbursement authorities Health care systems and prescribers Patients

13. Policy makers, EU institutions and individual governments They are setting the overall scene In EU pharmaceutical policy proposed by the European Commission and decided by European Parliament and Council, e.g. DG SANCO public health programme Do not cover healthcare and pricing and reimbursements - national responsibility EU regulation is based on presumption that commercial forces will supply the medicines we need Where the market does not deliver, then targeted action is taken, e.g. orphan drugs, paediatrics and Article 58 DG Research 7th framework programme gives directions on priority areas of research

14. Research-based pharmaceutical industry Drivers for decision-taking –Scientific opportunities –Market assessment and return on investment –Availability and required resources –Medical need Industry dilemma and challenge –Failure/attrition rate –High price for new medicines –Reward for innovation and price pressure Will the industry deliver the medicines we need?

15. Challenges

16. Regulatory agencies for market approval Decision on market approval based on quality, safety and efficacy Relative efficacy (comparative clinical trials) 20-25% of applications will not get market approval Are the approved medicines the medicines we need?

17. Pricing and reimbursement authorities Different systems and criteria in EU Member States No EU harmonisation/competence Decision based on ? and relative effectiveness and cost effectiveness Will their decisions secure access to medicines we need (Un)Equal access in EU

19. Health care systems and prescribers Health technology assessments –Example NICE in UK –Recommendation of use within NHS Regional and local drug committees –Recommendation on list of medicines for use –Local responsibilities for budget –Forcing hard priorities What is the criteria's for decision making? Prescribers have the final decision on witch medicines we need

20. Patients Historical patients passive in decision on therapy Probably a dramatic change in the future Budget constrains and priorities will make patients and there organisation more active Publication of clinical trials will create a demand for early access to new medicines Availability of information (Internet) Patients participate in benefit risk assessment Patients will move where they could receive the treatment

21. EMEA role in the need of medicines Research-based industry, not regulators (incl. EMEA) select therapeutic areas of interest and make individual drug development decisions However, regulators (and legislators) proactively facilitate and influence drug development by: Setting regulatory and scientific standards, making regulatory decision more predictable Introduce incentives (e.g. orphan drugs, paediatric drugs, SMEs) Specific collaborative programs: EMEA Road map 2010,US FDA critical path initiative, EU commission and industries initiative IMI

22. EMEA roadmap 2010 –Safety of medicinal products –Earlier availability of new medicinal products –Support to innovation –Transparency, communication and provision of information –Reinforcing the EU medicines network

23. Rapid access to new medicinal products and Support to innovation New regulatory tools for access –Conditional MA and accelerate assessment –Risk management plans –Benefit risk assessment more consistency and predictability Support to innovation –How to met the demand from a rapid scientific development –Scientific advice in drug development Urgent public health needs –Pandemic influenza vaccines

24. EMEA support to IMI Initiatives The Innovative Medicine Initiative (IMI) –Part of the 7 th Research framework program –Promote development innovative therapies –Partners: EU Commission, Academia, Patients Associations, EU Industry (including SMEs), Regulatory Authorities –Objectives: to make development process faster, efficient (reduce attrition), predictable and cheaper

25. IMI Initiative

27. Conclusion A shift to a growing elderly population will create a high need for health care in EU and need for new treatments Important to monitor the development of new medicines and identify gaps and needs If not market forces will fill the gaps governments or none profit organisations need to intervene Decision making and criteria's for regulatory approval is well defined with a long tradition and history Post approval decisions on different levels in member state is not harmonised leading to difference in availability A priority for EMEA is to support accesses to medicines and stimulate drug development Innovative medicine initiative (IMI )will contribute to an improved drug development process