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 Context/Background Pammoli, G-10 and EU Commission Reports The Lisbon and Barcelona European Councils: the “3% solution” Framework Programmes FP6 FP7 European and Developing Countries Clinical Trials Partnership (EDCTP)

3 Objectives of Priority Medicines Project Provide a methodology for identifying priority diseases with 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 aims to prioritise spending of public funds on areas of greatest public needs”

4 "Priority Medicines" Medicines which are needed to meet the priority health care needs of the population but which have not yet been developed. A “pharmaceutical gap” occurs when pharmaceutical treatments for a disease/condition: –does not yet exist OR –are likely to become ineffective in the future OR –are available but the delivery mechanism or formulation is not appropriate for the target patient group.

5 Generating a Preliminary List of Diseases and Gaps

6 Commonality of interest for Europe and the World Considerable Commonality of interest exists for chronic diseases –Antibacterial resistance & Pandemic Influenza –Ischemic Heart Disease, Diabetes, Cancer, Acute Stroke, Alzheimers and other dementias, Osteoarthritis, COPD, & Depression Social Solidarity needs for: –HIV/AIDS, TB, Neglected Diseases, Malaria, Maternal Haemorrhage

7 "Commonality of interest"

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

9 Pharmaceuticals and Children (See Chapter 7.3) Children subject to same diseases as adults BUT Prescribed medicines that are often not licensed or are "off label." Doses often only adjusted for weight but children differ in in PK & PD aspects Pediatric formulations needs for "adult medicines"

10 Research Gaps for Children and Medicines Clinical and pharmaceutical follow up of unlicensed and off-label use Specific medicines and formulations needed for some paediatric conditions especially paediatric AIDS Accurate diagnosis and treatment of early "marker diseases" in children needed

11 Obstacles to Research for Children and Medicines Problems in researching unlicensed and off- label use Specific childhood diseases are rare and the population changes rapidly with age Ethical and managerial issues in undertaking clinical trials in children Limited incentive for companies to exist as market small Limited incentive for research on use of off- patent medicines

12 Regulatory Approaches to Promoting Research on Children & Medicines US - Paediatric Labeling Rule (1994) & Best Pharmaceuticals for Children Act 2004 provides 6 months market exclusivity Europe – European Guidelines on paediatric clinical trials and Directive on GCP July These encourage only. 29 th September proposal creates a new expert committee, a requirement for data at authorization, 6 month patent extension, increased safety monitoring, EU inventory of needs & free advice from EMEA

13 Priority Research Needs for Children and Medicines In addition to regulatory responses research needed on: Off label and unlicensed use of off patent medicines Pathophysiology and risk factors for diseases affecting children Diagnostics to avoid under or over treatment of children Attitudes to medication usage that impede the proper use of medicines in children

14 Promoting Innovation and Removing Barriers Public Private Partnerships may be a vehicle to address market failure Dealing with pricing issues is critical to the future of the European pharmaceutical industry. Propose investigating differential pricing based on GNI per capita and efficacy measures 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

15 Role of Patients and their parents remains unclear Patients & parents 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 Patient organizations must address conflict of interest in funding

16 Conclusions 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 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

17 Priority Medicines Project For further questions, please contact:

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

19 Global Public Health Threats Antibacterial Resistance: For infectious diseases, the present burden in Europe is low removing incentives for research. Most antibiotics are inexpensive- removing incentives to create new antibiotics Antibacterials are widely misused creating resistance Less research on antibiotics could have profound consequences for future generations with the global increase in the spread of drug- resistant bacteria.

20 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

21 Global Public Health Threats (2) Pandemic Influenza: Overdue for a new pandemic Uptake of existing vaccines in Europe is poor compared to Canada, US, Korea and Australia Current capacity to produce either vaccines or antiviral medicines is not sufficient

22 Secondary Prevention of Cardiovascular Disease & Stroke Patients who have had a heart attack or stroke could reduce their risk of a repeat attack by 66% if they took 4 proven medicines. BUT uptake is low <20% The "polypill" using fixed dose combination of aspirin, statin, ACE inhibitor and beta- blocker or thiazide diuretic deserves further urgent study.

23 High burden, preventable diseases with pharmaceutical gaps Smoking-related conditions: Public health, anti-smoking policies are the key interventions Effective pharmaceutical interventions to stop smoking 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 and they are associated with an increased risk of adverse events.

24 High burden, preventable diseases with pharmaceutical gaps HIV/AIDS: There are particular "gaps" with regard to HIV formulations for children Support needed for HIV Vaccine Alcoholic liver disease: The overriding imperative should be to reduce the prevalence and incidence of alcohol abuse Need for translational research to convert basic science advances into products that can be used in clinical trials.

25 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

26 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

27 "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