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PRIORITY MEDICINES FOR EUROPE AND THE WORLD:

a public health approach to innovation

Hans V. HogerzeilDirector, Medicines Policy and Standards

WHO, Geneva

based on a WHO report by

Warren KaplanRichard Laing

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Objectives

• Provide a methodology for identifying pharmaceutical “gaps” from a public health perspective

• 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 fundson areas of greatest public needs

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Priority Medicines

• Medicines for priority health care needs of the population which have not yet been developed: "missing essential medicines"

• Pharmaceutical gap: when treatment for a disease/condition:– does not yet exist OR– will become ineffective soon OR– is available but the formulation is not appropriate for the target

patient group

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Generating a Preliminary List of Diseases and Gaps

Burden of disease rankingEU10, EU25

The world (including EU25)

Cochrane database of systematic reviews

Clinical efficacy

FINAL REPORT

Projectionsand trends

Socialsolidarity

PRELIMINARY LISTOF PRIORITY DISEASES AND

GAPS

IN DEPTH REVIEWS OF PRELIMINARY LIST OF DISEASES AND GAPS

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Pharmaceutical "Gap"Treatment of ACUTE Stroke (Outcome: Survival at end of treatment or follow-up, unless noted otherwise)

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

Rel

ativ

e R

isk

(<1

favo

rs p

lace

bo)

Various excitatory nerve amino acid antagonists

Ion channel,modulators

NMDAantagonists

Fibrinogendepleting agents

Gangliosides

Antiplatelettherapies

Streptokinaseurokinase( 7 days)Glycerol

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Example: no pharmaceutical gap

Secondary prevention of occlusive event (Stroke/MI) with antiplatelet therapy

0

0.5

1

1.5

2

2.5

. . . . . . . . . . . .

Rel

ativ

e ri

sk (

<1

favo

urs

pla

ceb

o)

Prior MI

Prior MI

Prior stroke All trials

Aspirin any dose

Dipyridamole

Sulfinpyrazole

Ticlopidine

Suloctidil

Picotamide

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Commonality of interestEUROPE THE WORLD

?? ??

?? ??

* Includes bladder, breast, cervical,colon, uterine, lungliver, mouth, oesophageal, ovarian, pancreatic,prostate, stomach cancer and leukemias, melanomas,lymphatic cancers and myelomas

** "Cerebrovascular disease"

*** Chagas disease, Dengue, Leishmaniasis, lymphaticfilariasis, Onchocerciasis, Schistosomiasis, Trypanosomiasis

10% 8% 6% 4% 2% 0 2% 4% 6% 8% 10%Antimicrobial Resistance

Pandemic Influenza

Ischaemic Heart Disease

Diabetes Mellitus

Cancer*

Acute Stroke**

HIV/AIDS

Tuberculosis

Neglected Diseases***

Malaria

Alzheimer and other dementias

Osteoarthritis

COPD

Alcohol use disorders

Unipolar depression

Maternal hemorrhage

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Global Public Health Threats (1)

Antibacterial Resistance

• Low burden of infectious diseases in Europe removes incentive for R&D

• Most antibiotics are inexpensive – also removes incentives to create new antibiotics

• Antibacterials are widely misused, creating resistance

• Little R&D on antibacterials has consequences for future generations (global spread of drug-resistant bacteria).

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The rise of antibacterial resistance and the decline in innovation

The proportion of MRSA among The proportion of MRSA among positive blood cultures of S.aureus positive blood cultures of S.aureus in in England & Wales, 1989-2002

0

5

10

15

20

1983-1987 1988-1992 1993-1997 1998-2002

No. o

f FDA

app

rove

d an

tibac

teria

l NM

Es

Antibacterial new molecular entities approved for use in the United States 1983-2002

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Global Public Health Threats (2)

Pandemic Influenza

• Overdue for a new pandemic

• Poor uptake of existing vaccines

• Insufficient current capacity to produce vaccines or antiviral medicines

Rates of vaccine distribution per 1000 total population by country

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Secondary prevention of cardiovascular disease & stroke: lack of suitable formulation

• 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" in fixed dose combination (aspirin, statin, ACE inhibitor and beta-blocker or thiazide diuretic) deserves further urgent study

• No real incentive for FDC/R&D as most are generics

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High burden, preventable diseases

with pharmaceutical gaps

Smoking-related conditions • Public health anti-smoking policies and effective medicines needed

Treatment of acute stroke • Major basic/clinical research effort needed; most agents ineffective

HIV/AIDS • HIV formulations for children, HIV vaccine

Alcoholic liver disease • Reduce prevalence and incidence of alcohol abuse; translate basic

science advances into products for trials

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High burden diseaseswithout 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

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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• Existing antidepressants works well for adult depression• Gaps in understanding biology of depression and its

treatments in these groups

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Neglected diseasesLack of EU support for translational research for market failure diseases

Malaria • Lack of experimental models for medicines discovery R&D

Tuberculosis

• More FDCs for 2nd 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 major advance in public health

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Special needs for women, children, and the elderly

• All these groups neglected in drug development • Complicated by different physiology & metabolism• Recent improvements for women and children, but• Considerable gaps remain for the elderly, who use the

most medicines

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Other issues

• Public Private Partnerships may be a vehicle to address market failure; need more "public"

• Pricing issues are critical to the future of the European pharmaceutical industry; prices should reward innovation

• Role of patients is unclear but likely to increase• Some regulatory barriers to innovation exist and need

to be reduced

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Conclusion (1): Different types of gaps

• Global public health threats• High burden of preventable diseases, but

– no suitable formulation– no biomarkers– therapy could be improved

• Neglected diseases– translational research

• Special needs for women, children, elderly

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Conclusion (2)

• 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, cardiovascular disease and neglected diseases

• Pricing issues and regulatory barriers to innovation strongly affect the European industry

• The EU needs to find a way to support translational research for market failure pharmaceutical gaps

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Priority Medicines Project

For further questions, please contact:

laingr@who.int

+41-22-791-4533

www.who.int/medicineshttp://mednet3.who.int/prioritymeds/report/index.htm