1 PRIORITY MEDICINES FOR EUROPE AND THE WORLD A report prepared by WHO for the Netherlands Government by Warren Kaplan Richard Laing and Saloni TannaMarjolein Willemen Eduardo SabatéMonique Renevier Joyce WilsonLisa Greenough Ann WilberforceKathy Hurst

2 Priority Medicines Project 1.Background/Introduction 2.Priority Setting 3.Methods 4.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

7 Priority Medicines Project 1.Background/Introduction 2.Priority Setting 3.Methods 4.Results/Conclusions

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

9 Priority Medicines Project 1.Background/Introduction 2.Priority Setting 3.Methods 4.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 1.Background/Introduction 2.Priority Setting 3.Methods 4.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 The proportion of MRSA among positive blood cultures of Staphylococcus Aureus in England &Wales Antibacterial new molecular entities approved for use in the United States

17 Global Public Health Threats (2) 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 Rates of vaccine distribution per 1000 total population by country

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" diseases Lack 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 Conclusions Priority 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:

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

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 ( ) The UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) The US National Institutes of Health (NIH) (1998)