Transcript Presentation made to EPPOSI conference on

PRIORITY MEDICINES
FOR EUROPE AND THE
WORLD
A report prepared by WHO for the
Netherlands Government
by
Warren Kaplan
Richard Laing
and
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Saloni Tanna
Eduardo Sabaté
Joyce Wilson
Ann Wilberforce
Marjolein Willemen
Monique Renevier
Lisa Greenough
Kathy Hurst
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)
2
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”
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"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
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– are available but the delivery mechanism or
formulation is not appropriate for the target patient
group.
Generating a Preliminary List
of Diseases and Gaps
Cochrane database of
systematic reviews
Clinical efficacy
Burden of disease ranking
EU10, EU25
The world (including EU25)
Projections
and trends
PRELIMINARY LIST
OF PRIORITY DISEASES AND
GAPS
IN DEPTH REVIEWS OF PRELIMINARY LIST OF DISEASES AND GAPS
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FINAL REPORT
Social
solidarity
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
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"Commonality of interest"
EUROPE
10%
??
??
8%
6%
4%
THE WORLD
2%
0
2%
4%
6%
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
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Unipolar depression
Maternal hemorrhage
8%
10%
??
??
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
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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"
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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
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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 offpatent medicines
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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 2002.
These encourage only.
• 29th 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
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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
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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
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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
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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
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Priority Medicines Project
For further questions, please contact:
[email protected]
[email protected]
+41-22-791-4533
http://mednet3.who.int/prioritymeds/report/index.htm
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Differential Pricing: Indicative prices in
US$/annum of highly active antiretrovirals
(HAART) and a new hypothetical regimen in
countries of variable wealth
30000
United Kingdom
France
Italy
25000
15000
Slovenia
Czech Republic
10000
Latvia
5000
Indicative price existing treatment
26076
23225
15000 20000 25000
Per capita GNI $US
18
22783
19831
15627
12620
5000
10881
6199
4921
3744
3477
2500
2566
2557
2000
2401
2125
1959
1000
1637
1214
993
500
855
607
441
200
763
Russian Fed.
Kazakhstan
Philippines
Georgia
India
294
267
Mali
0
487
Indicative price $US
Spain
20000
Indicative price new drug
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 drugresistant bacteria.
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The Rise of Antibacterial Resistance
and the Decline in Innovation
Antibacterial new molecular entities
approved for use in the United States
1983-2002
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No. of FDA approved antibacterial NMEs
The proportion of MRSA among positive
blood cultures of Staphylococcus Aureus in
England &Wales1989-2002
15
10
5
0
1983-1987
20
1988-1992
1993-1997
1998-2002
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
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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 betablocker or thiazide diuretic deserves
further urgent study.
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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.
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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.
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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
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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:
•
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Gaps in understanding biology of depression and its
treatments in these groups
"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
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