PRIORITY MEDICINES FOR EUROPE AND THE WORLD

1. PRIORITY MEDICINES FOR EUROPE AND THE WORLD A report prepared by WHO for the Netherlands Government by Warren Kaplan Richard Laing and • Saloni Tanna Marjolein Willemen • Eduardo Sabaté Monique Renevier • Joyce Wilson Lisa Greenough • Ann Wilberforce Kathy Hurst

2. Priority Medicines Project • Background/Introduction • Priority Setting • Methods • Results/Conclusions

3. Context/Background • Pammoli, G-10 and EU Commission Reports • Europe was “lagging behind in its ability to generate, organize, and sustain innovation processes that are increasingly expensive and organizationally complex.” • The Lisbon and Barcelona European Councils: the “3% solution” • Framework Programmes FP6 FP7 • European and Developing Countries Clinical Trials Partnership (EDCTP)

4. Objectives of Priority Medicines Project • Provide a methodology for identifying pharmaceutical “gaps” from a public health perspective, for Europe and the World . • Provide a public-health based pharmaceutical R&D agenda for use by the EU in the 7th Framework Programme, “Good public policy should spend public funds on areas of greatest public needs”

5. "Priority Medicines" • Medicines which are needed to meet the priority health care needs of the population but which have not yet been developed. • “pharmaceutical gap”: when treatment for a disease/condition: • does not yet exist OR • will become ineffective soon OR • is available but the delivery mechanism or formulation is not appropriate for the target patient group.

6. What this Report does not address • Health system issues such as access or quality of care, or logistical or sociological barriers. • Underlying risk factors which can be considered a major cause of morbidity or mortality. • Availability of diagnostics or medical devices • Relationship between trade, pricing, intellectual property, as this is the subject of the WHO Commission on Intellectual Property Rights, Innovation and Public Health. (See http://www.who.int/intellectualproperty/en/)

7. Priority Medicines Project • Background/Introduction • Priority Setting • Methods • Results/Conclusions

8. Source: Adapted from Dr. Kenneth Hammond, Univ. Colorado, USA & NICE (UK) Prioritization must be multifactorial

9. Priority Medicines Project • Background/Introduction • Priority Setting • Methods • Results/Conclusions

10. Generating a Preliminary List of Diseases and Gaps

11. Pharmaceutical "Gap"

12. Example of an absent pharmaceutical gap

13. Priority Medicines Project • Background/Introduction • Priority Setting • Methods • Results/Conclusions

14. "Commonality of interest"

15. Global Public Health Threats Antibacterial Resistance: • Infectious diseases: low burden in Europe removes incentive for R&D • Most antibiotics are inexpensive- removing incentives to create new antibiotics • Antibacterials are widely misused creating resistance • Little R&D on antibacterials has consequences for future generations with the global increase in the spread of drug-resistant bacteria.

16. The Rise of Antibacterial Resistance and the Decline in Innovation The proportion of MRSA among positive blood cultures of Staphylococcus Aureus in England &Wales1989-2002 Antibacterial new molecular entities approved for use in the United States 1983-2002

17. Global Public Health Threats (2) Rates of vaccine distribution per 1000 total population by country Pandemic Influenza: • Overdue for a new pandemic • Uptake of existing vaccines is poor • Current capacity to produce either vaccines or antiviral medicines is not sufficient

18. Secondary Prevention of Cardiovascular Disease & Stroke • Patients with a heart attack or stroke could reduce their risk of a repeat attack by 66% by taking 4 medicines (good evidence) • Yet uptake is low <20% • The "polypill" using fixed dose combination (aspirin, statin, ACE inhibitor and beta-blocker or thiazide diuretic) deserves further urgent study.

19. High burden, preventable diseases with pharmaceutical gaps Smoking-related conditions: • Public health anti-smoking policies are key interventions • Effective pharmaceutical interventions are needed. Treatment of acute stroke: • A major basic and clinical research effort is required as the current treatment of acute stroke is unsatisfactory. • Most agents are not effective: associated with increased risk of adverse events.

20. High burden, preventable diseases with pharmaceutical gaps HIV/AIDS: • HIV formulations for children urgently needed • HIV Vaccine Alcoholic liver disease: • Reduce prevalence and incidence of alcohol abuse • Translational research to convert basic science advances into products for clinical trials.

21. High burden diseases without bio markers Osteoarthritis: • New diagnostics, biomarkers and imaging technology will help determine who is likely to get osteoarthritis, and the response to treatment Alzheimer disease: • More sensitive, reliable and valid tools for detecting changes in normal ageing and the onset of early Alzheimer disease needed. • Lack of surrogate markers remains a major barrier in the clinical development of AD drugs

22. High burden diseases where existing therapies could be improved Cancer : • More capacity (infrastructure and human resources) and coordination to conduct comparative clinical trials • Continue to invest in basic research into cancer biology Diabetes: • Heat stable insulin would be a major advance in public health • Gaps in basic biology, stem cell research, transplantation research Depression in adolescents & elderly: • Gaps in understanding biology of depression and its treatments in these groups

23. "Neglected" diseasesLack of EU support for translational research for market failure diseases Malaria: • Lack of experimental models for medicines discovery and development. Tuberculosis: • More FDCs for second-line treatment of multidrug-resistant TB & Diagnostics Leishmaniasis, trypanosomiasis, Buruli ulcer: • Most of the medicines being used are "old" and often dangerous Post-partum haemorrhage: • Major cause of maternal mortality in developing countries, heat stable oxytocin would be a major advance in public health for women

24. Special Needs for Women, Children, and the Elderly • All groups neglected in drug development • Complicated by different physiology & metabolism • Recent improvements in situation of women and children • Considerable gaps remain for the elderly who use the most medicines

25. Promoting Innovation and Removing Barriers • Public Private Partnerships may be a vehicle to address market failure • Pricing issues are critical to the future of the European pharmaceutical industry. Propose investigating differential pricing based on GNI per capita and efficacy measures. Reseach prospective price setting. • EMEA, FDA, Rawlins and Industry have all proposed similar measures to remove barriers • Comparative trials provide critical information on head to head comparisons. Use of European databases may facilitate such studies

26. Differential Pricing: Indicative prices in US$/annum of highly active antiretrovirals (HAART) and a new hypothetical regimen in countries of variable wealth

27. Role of Patients remains unclear • Patients have speeded innovation e.g. AIDS and Orphan diseases • Valuable role in treatment guideline development emerging e.g. NICE • Patients play important role in ethical & hospital committees e.g. IRB & DTCs • Will now be part of CSM in UK • Future role likely to be important and growing

28. ConclusionsPriority Medicines for Europe and the World • Commonality of interest exists for chronic diseases between Europe and the World • Priorities can be set based on evidence, trends and projections and social solidarity • Pharmaceutical gaps exist as a result of biological challenges and market failure • Highest priorities are antibacterial resistance, influenza, smoking cessation and neglected diseases • Pricing issues and barriers to innovation strongly affect the European industry • The EU needs to find a way to support translational research for market failure pharmaceutical gaps

29. Priority Medicines Project For further questions, please contact: laingr@who.int wak22@comcast.net +41-22-791-4533 http://mednet3.who.int/prioritymeds/report/index.htm

30. 100% Untreatable with existing interventions including incurable chronic conditions 4 1 2 3 Combined efficacy of a mix Treatable with current Treatable with Few treatments of all mix of interventions existing interventions available, better available but obstacles to formulations and interventions access exist delivery mechanisms needed 0% Population coverage 0% 100% with current mix Maximum achievable of interventions coverage Identifying gaps (unmet therapeutic needs):a public health perspective

31. International organizations and less formal groups have developed methods for prioritizing health research • The Commission on Health Research for Development (1990) • The World Development Report (1993 ) • The Ad Hoc Committee on Health Research (1996) • The Global Forum for Health Research (2000) • WHO-IFPMA Round Table (2000-2001) • The UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) • The US National Institutes of Health (NIH) (1998)