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The Innovative Medicines Initiative (IMI)

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• nly the call documents and topics represent the
• fficial position of the IMI Joint Undertaking.

The Innovative Medicines Initiative (IMI)

Information Day

Brussels 30 April 2008

The Innovative Medicines Initiative (IMI)

Alain Vanvossel IMI JU Interim Executive Director European Commission, Head of Unit, DG RTD

The Innovative Medicines Initiative (IMI)

Jonathan Knowles IMI Board Chair EFPIA RDG Chair Head of Group Research, Roche

The Innovative Medicines Initiative (IMI)

Mary Baker President of the European Federation of Neurological Associations

The Innovative Medicines Initiative (IMI)

Irene Norstedt IMI JU European Commission, Head of Sector, DG RTD

The Innovative Medicines Initiative (IMI)

History, Concept and Organisation

Irene Norstedt

2

History

Lisbon Strategy Europe most competitive and dynamic knowledge-based economy by 2010 2000 2004 European Technology Platforms stakeholders under the lead of industry develops Strategic Research Agendas addressing bottlenecks to competitiveness 2007 2008 7th Framework Programme for Research Major novelties: European Research Council and Joint Technology Initiatives Establishment of the Joint Undertakings to implement the Joint Technology Initiatives

3

Joint Technology Initiatives

Long term public-private partnerships in research at European level Coordinated research efforts responding to industry needs Focus on fields of high industrial and policy relevance Building on European Technology Platforms To be implemented through new legal entities - Joint Undertakings 20 December 2007 Council Decision to establish four Joint Undertakings: IMI, Clean Sky, ARTEMIS, ENIAC

4

COUNCIL REGULATION (EC) No 73/2008

• f 20 December 2007

setting up the Joint Undertaking for the implementation of the Joint Technology Initiative on Innovative Medicines Official Journal 04.02.2008

5

2 Billion EURO

1 Billion Euro 1 Billion Euro

Public Private Partnership

6

• IMI aims at removing major bottlenecks in drug development, where

research is the key

• With the long term goal to re-invigorate the European bio-pharmaceutical

sector and foster Europe as the most attractive place for pharmaceutical R&D, thereby, in the long term, enhancing access to innovative medicines for patients.

• IMI will support ‘pre-competitive pharmaceutical research and development’,

in order to accelerate the development of safer and more effective medicines for patients.

• No new medicines will be developed as such as the focus shall be on the

delivery of new approaches, methods and technologies, improve knowledge management of research results and data, and support the training of professionals.

7

• IMI will support research activities following open and competitive calls for

project proposals, peer review evaluation and the conclusion of Grant Agreements and Project Agreements.

• The research will be funded by a combination of a financial contribution from

the IMI JU to academia, SMEs, patients associations, etc. and a contribution ‘in kind’ from the participating EFPIA member companies.

• The call and evaluation process is tailor made to serve the objectives of IMI
• The IMI IP policy is aligned with the objectives of IMI - findings (Foreground)

must be widely and readily available for research into the discovery and development of medicines

• The IMI IP policy provides incentives for all actors to participate (i.e. the
• wnership interest, direct exploitation and the fair return on investment must

be preserved)

8

• IMI shall foster collaboration between all stakeholders, e.g. industry,

public authorities (including regulators), organisations of patients, academia and clinical centres.

• IMI will launch one call for proposals 2008 – today!!!
• Topics included in the first call are based on IMI’s Scientific Priorities

for 2008 and are derived from the IMI Research Agenda.

• Areas in the IMI Research Agenda not addressed in 2008 will be

addressed in consecutive calls.

9

Executive Director (+ staff)

IMI Governance IMI JTI = IMI JU + External Advisory Groups

Stakeholder Forum IMI States Representatives Group

IMI Joint Undertaking (IMI JU)

Scientific Committee Governing Board

10

IMI Joint Undertaking

IMI Joint Undertaking (IMI JU)

Scientific Committee Governing Board

2 Founding Members Overall responsability for the operations of IMI Responsible for day- to-day management 15 members Scientific Advise to the Board

Executive Director (+ staff)

11

IMI External Advisory Bodies

Stakeholder Forum IMI States Representatives Group

Annual meeting open to all stakeholders Communication One representative per Member and Associated State Interface with stakeholders in MS/AS and communication Chair observer in Governing Board

12

State of Play

• Council Regulation entered into force 7 February 2008
• Governing Board meetings 3 March and 29 April 2008
• Interim Executive Director has been appointed
• Process for setting up the Scientific Committee has

started by inviting proposal for candidates from the Member and Associated States

• Process for setting up the IMI States Representatives

Group has started by inviting Member and Associated States to nominate representatives

13

State of Play

Starting the operations

• Launching the first call for proposals 30 April 2008
• Start recruitment Executive Director and key staff
• Set up office in Brussels

14

Expected outcomes

• Modernisation of the development process of medicines
• More and better quality jobs for scientists, reversing the brain drain
• Better European Expertise and know how in technologies to attract

biomedical R&D investment to Europe

• Stronger competitive advantage for smaller companies (SMEs, spin-offs and

start ups) by collaboration with a multitude of stakeholders to enhance Europe’s competitiveness.

The Innovative Medicines Initiative (IMI)

The IMI Call and Evaluation Process Ian Ragan IMI Advisor to EFPIA

• Rules for participation
• Eligibility for funding
• Rules for submission
• Call process

– Description of call topics – Submission of expressions of interest – Submission of full project proposals – Peer review evaluation

• Timelines
• Topics

Agenda

Rules for Participation in IMI Consortia

• Any entity carrying out work relevant to the IMI

JU in a Member State or country associated with the 7th Framework Programme

• Anyone else with the agreement of the IMI JU

BUT

• Not all participating entities are eligible for

funding

Eligible Consortia

• The IMI JU supports consortia who submit

applications in response to a call

• Consortia must contain:

– At least 2 legal entities eligible to receive funding – At least 2 research-based pharmaceutical companies who are members of EFPIA – All 4 entities must be independent of each

• ther

Eligibility for IMI funding – EFPIA companies – Other companies not falling within the EU definition of SMEs – Academia – SMEs (EU definition) – Patient Organisations – Other non-for-profit legal entities Non-eligible for funding Eligible for funding

Direct eligible costs

• Actual
• Incurred by the claimant
• Incurred during the project
• Incurred for work in a Member State or

country associated with FP7

• Incurred for the achieving the
• bjectives of the project

Total eligible costs Direct Eligible Costs These apply equally to all participants - to those who receive funding and to the EFPIA participants to calculate their in-kind contribution Indirect Costs (max 20% of Direct Eligible Costs, excl. subcontracting)

Upper Funding Limits

(for participants eligible for funding by the IMI JU) Other Activities, including Management and Training Activities Maximum 100%

• f total eligible

costs Research Activities Maximum 75%

• f total eligible

costs

IMI Call Process is Different from the 7th Framework Programme Process

• 1. Research topics are approved by the IMI Governing

Board (EFPIA and European Commission) based on proposals from the EFPIA Research Directors Group and after consultation with IMI Member State Representatives & IMI Sci. Committee

• 2. A private consortium (the EFPIA Consortium) is

established for each topic & a coordinator and deputy are proposed who will lead the full Consortium

IMI Call Process is Different from the 7th Framework Programme Process

• 3. Applicant Consortia submit Expressions of Interest

without the involvement and participation of the EFPIA Consortia (stage 1)

• 4. For each topic, the best selected Applicant

Consortium joins the EFPIA Consortium to form a Full Project Consortium

• 5. The Full Project Consortium submits a Full Proposal to

stage 2 of the peer review process

Call Research Agenda Call Topics Annual Implementation Plan

Call definition

Call & Evaluation Process

Call definition

Description of the Call Topics

• 1. Title
• 2. Project description
• 3. Key deliverables of the project
• 4. EFPIA member companies participating in the

project

• 5. Role of EFPIA participants in the project
• 6. Duration of the project
• 7. Total in kind contribution from the EFPIA member

companies

• 8. Expectations from the Applicant consortium

(science and budget guideline)

Description of the call topics 2

• IMI research projects will often be

multidisciplinary and addressing translational medicine challenges

• Integrated approaches between non-clinical

and clinical disciplines are often required

• The successful Applicant Consortium is expected

to include expertise for all aspects of the areas mentioned in the description of the call topics

Call Research Agenda Call Topics Annual Implementation Plan

Call definition

Expression of Interest 1st Peer Review Invitation to Submit Full Project Proposal

Stage 1: Scientific excellence

Call & Evaluation Process

Stage 1

≈ 5 months

Description of the Expression of Interest

1. Scientific Case

1. Approaches to meet the project objectives (2 pages) 2. Composition of the Applicant Consortium (1/2 page per member) 3. Unique features and complementarities of the Consortium (1 page) 4. Summary work plan (2 pages)

2. Declaration of ethical issues (1/2 page) 3. Provisional budget plan

1. Estimated cost per Consortium member 2. Estimated requested IMI contribution

Written by the Applicant Consortium: i.e. academia, SMEs, regulators, patients organisations (without EFPIA)

Peer Review Stage 1

• Peer Review Committees

– Ad hoc experts relevant to the call topics – EFPIA Consortia co-ordinators participate in evaluation of Expressions of Interest – For 2009 and beyond, Standing Peer Review Committees (one per Pillar of the Strategic Research Agenda) assisted by ad hoc experts

• Responsibility

– To evaluate science of Expressions of Interest and select the winning Applicant Consortium for each topic

Evaluation of the Expressions of Interest

Four categories that will be scored:

• Scientific and/or technological excellence
• Partnership Case
• Quality of the Applicant consortium as a whole
• Quality and soundness of the work plan, including budget

First two will have thresholds One category that will not be scored:

• Any other remarks including ethical issues

Call Research Agenda Call Topics Annual Implementation Plan

Call definition

Expression of Interest 1st Peer Review Invitation to Submit Full Project Proposal

Stage 1: Scientific excellence

Full Project Proposal 2nd Peer Review

Stage 2: Feasibility and scientific excellence

Call & Evaluation Process

Stage 2

≈ 5 months ≈ 3 months

Description of the Full Project Proposal

• Written jointly by the members of the EFPIA

Consortium and the winning Applicant Consortium

• Full description of research activities

– What, who, when, and how much

• Will need a draft Project Agreement before

submission

– IPR sharing agreed between all partners

• Expectation of high probability of success

Written by the Full Project Consortium: i.e. academia, SMEs, patients organisations with EFPIA companies

Peer Review Stage 2

• Peer Review Committees

– Ad hoc experts relevant to the call topics

• Same as reviewed the Expressions of Interest

BUT

• Addition of experts on ethics as needed
• No involvement of EFPIA Consortia co-ordinators

– Standing Peer Review Committees foreseen for future years

• Responsibility

– To evaluate Full Proposals based on science and feasibility

Evaluation of the Full Project Proposal

Evaluation will likely include consideration of the following aspects:

– Scientific and/or technological excellence – Consistency with the original Expression of Interest

• Scope and composition of the consortia

– Project implementation plan – Draft Project Agreement – Potential impact of the project results

Categories will be graded Excellent, Acceptable (subject to adjustment to points raised), or Non- acceptable

Call Research Agenda Call Topics Annual Implementation Plan

Call definition

• 1. Project Agreement
• 2. Grant Agreement

Contract Execution

Call & Evaluation Process

Expression of Interest 1st Peer Review Invitation to Submit Full Proposal

Stage 1: Scientific excellence

≈ 5 months

Full Project Proposal 2nd Peer Review

Stage 2: Feasibility and scientific excellence ≈ 3 months ≈ 2 months

Tentative timelines for First Call

May June July August Sept October Nov. Dec. January February Publication of Call Submission period for Expressions of Interest Evaluation Stage 1 Submission period for Full proposals Evaluation Stage 2 Negotiation, signature of Grant Agreements, first payments

April 30th July 15th

Topics for the First Call

• 1. Improved predictivity of immunogenicity 13m/5y
• 2. Non-genotoxic carcinogenesis 2.5m/2y plus 10m/3y
• 3. Expert systems for in silico toxicity prediction 5m/5y
• 4. Improved predictivity of non-clinical safety evaluation 10m/3y
• 5. Qualification of Translational safety biomarkers

21m/5y

• 6. Strengthening the monitoring of benefit/risk 15m/5y
• 7. Islet cell research 10m/5y
• 8. Surrogate markers for vascular endpoints 20m/5y
• 9. Pain research

7.5m/5y

• 10. New tools for the development of novel therapies in psychiatric disorders 10m/5y
• 11. Neurodegenerative disorders 7.5m/5y
• 12. Understanding severe asthma 12.5m/5y
• 13. COPD Patient Reported Outcomes 2m/1y plus 8m/5y
• 14. European Medicines Research Training Network 5m/7y
• 15. Safety sciences for medicines training programme 3m/5y
• 16. Pharmaceutical medicine training programme 4m/5y
• 17. Integrated medicines development training programme 3m/5y
• 18. Pharmacovigilance training programme 3.5m/5y

EFPIA Commitment: 172.5m Typical project 15m euros Majority 5y duration 5-10 EFPIA partners/project

The Innovative Medicines Initiative (IMI)

http://imi.europa.eu www.imi-europe.org

The Innovative Medicines Initiative (IMI)

COFFEE BREAK

The Innovative Medicines Initiative (IMI)

QUESTIONS AND ANSWERS

The Innovative Medicines Initiative (IMI)

LUNCH BREAK

Launching the 2008 IMI scientific programmes

Janez Potočnik European Commissioner for Science and Research Arthur Higgins EFPIA President, CEO of Bayer HealthCare

The Innovative Medicines Initiative (IMI)

An Overview of the 2008 Call Topics

Jonathan Knowles Chair, IMI Board IMI Launch, April 30th 2008

The Research Focus of IMI

Discovery research Preclinical develop. Translational medicine Clinical develop. Pharmaco

• vigilance

Predictive pharmacology Predictive toxicology

Efficacy Safety

Discovery research Preclinical develop. Translational medicine Clinical develop. Pharmaco

• vigilance

Discovery research Preclinical develop. Translational medicine Clinical develop. Pharmaco

• vigilance

Predictive pharmacology Predictive pharmacology Predictive toxicology Predictive toxicology

Efficacy Safety

Identification

• f biomarkers

Identification

• f biomarkers

Validation of biomarkers Validation of biomarkers Benefit/Risk assessment with regulatory authorities Benefit/Risk assessment with regulatory authorities Patient recruitment Patient recruitment

Knowledge Management Education & Training

Cancer Brain Disorders Metabolic Diseases Predictive pharmacology Predictive toxicology Identification and validation of biomarkers Patient recruitment Regulatory Risk assessment

Efficacy and Safety are often disease specific

Inflammatory Diseases Infectious Diseases

IMI First Call: 18 Call Topics

• 5 on safety prediction
• 1 on pharmacovigilance
• 2 on diabetes
• 3 on brain disorders
• 2 on pulmonary diseases
• 5 on Education & Training

Strong industry commitment

€3,5 24 Pharmacovigilance Training Programme 18 €3 24 Integrated Medicines Development Programme 17 €4 24 Pharmaceutical Medicine Training Programme 16 €3 24 Safety Sciences for Medicines Training Programme 15 €5 24 European Medicines Research Training Network 14 €10 9 COPD Patient Reported Outcomes 13 €12,5 10 Understanding Severe Asthma 12 €7,5 14 Neurodegenerative Disorders 11 €10 13 New Tools for the Development of Novel Therapies in Psychiatric Disorders 10 €7,5 12 Pain Research 9 €20 7 Surrogate Markers for Vascular Endpoints 8 €10 11 Islet Cell Research 7 €15 15 Strengthening the Monitoring of Benefit/Risk 6 €21 12 Qualification of Translational Safety Biomarkers 5 €10 11 Improved Predictivity of non-clinical Safety Evaluation 4 €5 10 Expert Systems for in silico Toxicity Prediction 3 €12,5 8 Non-genotoxic Carcinogenesis 2 €13 12 Improve Predictivity of Immunogenicity 1 In-kind (millions) Companies

Title

#

Discovery research Preclinical develop Translational medicine Clinical development Pharmaco- vigilance

We cannot do it without the stakeholders

Academia Policy Makers Healthcare Professionals Regulators Biopharma Industry

Patients

SMEs

The Innovative Medicines Initiative (IMI)

http://imi.europa.eu www.imi-europe.org

IMI First Call Topics

Philippe Cupers IMI JU European Commission, DG RTD Ian Ragan IMI Advisor to EFPIA

The Innovative Medicines Initiative (IMI)

IMI Safety and Pharmacovigilance Calls

The Innovative Medicines Initiative (IMI)

IMI Safety Calls Salah-Dine Chibout

Head of Exploratory Development Europe Global Head Investigative Toxicology at Novartis

Goals of the IMI Safety Projects

• Generate and improve cutting-edge technologies to

devop safer drugs for human.

• Develop methods and acquire knowhow in Europe to

lower the late attrition rate of drugs in development.

• Develop better tools for monitoring safety of drugs at

all stages of drug development – from discovery through clinical development and registration to routine use of drugs.

• The ultimate goal is the improvement of the patients‘

safety and benefit.

Topics covered by the Safety Projects

• Expert systems for in silico toxicity prediction.
• Non-genotoxic carcinogenesis.
• Immunogenicity of biotherapeutics in man.
• Qualification of translational safety biomarkers.
• Improved predictivity of non-clinical safety evaluation

(presented by Thomas Singer).

• Strengthening the monitoring of benefit/risk assessment

(presented by Liz Swain).

Expert Systems for in Silico Toxicity Prediction

• In vivo and in vitro studies generate a lot of data that

can be used to model prediction of toxicity from the chemistry of the molecule.

• Early in silico prediction of such cases would increase

the quality of drug candidates and ensure a lower attrition rate before and during the first GLP animal studies.

• This would also reduce the number of animals (3Rs)

used in preclinical studies necessary to select drug candidates.

Expert Systems for in Silico Toxicity Prediction:

• Rationale

Expert Systems for in Silico Toxicity Prediction:

• Principle

N OH O H N O N OH

Chemical structure & features Bibliography Public databases Expert system Algorithms Computation

N

Query about a new structure Toxicity alert New structure or limited early toxicity study New Report Pharma reports

Expert Systems for in Silico Toxicity Prediction: Deliverables

• A toxicological database with high quality in vivo and in vitro
• data. This repository will form the basis of prediction model

development.

• Construction of prediction models for selected in vivo endpoints

to identify compound liability for target organ toxicity.

• A successful outcome will initiate the validation of these

prediction models. The validation experience will be shared between companies and with regulators.

• Reduction of total animal usage, according to the 3Rs.

Nongenotoxic Carcinogenesis (NGC)

Nongenotoxic Carcinogenesis (NGC):

• Rationale
• Need to better understand predictive value of rodent bioassay for

human cancer risk assessments of pharmaceutical drugs.

• Need accurate and well validated early biomarkers that can reliably

predict later cancer development.

• Exploit recent advances in understanding carcinogenesis to identify

early mechanisms and biomarkers of rodent NGC.

• 3Rs: gain maximum benefit from animal studies by sharing IMI

consortia knowledge and tissue archives.

Nongenotoxic Carcinogenesis (NGC):

• Goals & deliverables
• 2 year Exploratory Phase

– evaluate utility of novel tools & models for identifying mechanisms & biomarkers of rodent NGC.

Examples:

• Epigenomic profiling of tissues & tumours.
• Transgenic & humanised mouse models.
• Blood-based surrogate markers (Circulating tumour cells & methylated DNA).
• 3 year Confirmatory Phase

– validation of mechanistic hypotheses & cause-effect relationships. – predictive value & clinical relevance of biomarkers. – generate novel database for rodent tumour molecular profiles.

Prediction of Immunogenicity

Prediction of Immunogenicity Background

• Immunogenicity is the unwanted immune response (anti-

drug antibodies) to a Biotherapeutic.

• Immunogenicity is key to development of Biotherapeutics,

since it affects patient safety, drug efficay and study interpretation.

• Unmet need to predict and minimize immunogenicity in

man.

Prediction of Immunogenicity Current Issues

• 1. Limited comparability of immunogenicity data between

assays & companies.

• 2. Amount of data within individual companies too limited

– to understand factors or patterns favouring immunogenicity. – to verify predictive tools and minimization strategies.

• 3. Lack of reliable prediction methods for immunogenicity

potential of compound, clinical consequences and susceptibility of patient to develop immunogenicity (stratification).

• 4. Limited literature and guidance available.

• 1. Drug class-specific standardization programme in order to

improve comparability and quality of data defining immunogenicity positives vs. negatives.

• 2. Database of immunogenicity-relevant data of consortium

compounds:

• to identify factors or patterns favouring immunogenicity.
• to evaluate value of existing predictive tools and

minimization strategies.

• 3. Improved tools to predict immunogenicity in man, based on

at least 5 selected compounds (in-silico, in-vitro, animal models and stratification markers).

• 4. Publish recommendations.

Prediction of Immunogenicity Goals & Deliverables

Translational Safety Biomarkers Qualification

Translational Safety Biomarkers Qualification Background

• A lack of specific and sensitive blood and urine tests

(=peripheral biomarkers) for safety monitoring.

• Example: A histopathology safety signal is seen in

preclinical toxicity studies but there is no adequate monitoring method available in humans = lost

• pportunity to further explore clinical development

and potential human health benefits of this drug.

Translational Safety Biomarkers Qualification Background

• 3 target organs will be selected, which are

criticial for drug-induced injury:

• Kidney: Current standards (Serum Creatinine,

BUN) are only increased when 50-60% of the kidney function is lost.

• Liver: Current standards (AST, ALT, Bilirubin) are

not specific and do not predict, who will recover and who will develop fulminant liver disease.

• Vascular System: There are currently no

biomarkers to monitor drug-induced vascular injury in human.

Translational Safety Biomarkers Qualification Goals

• To evaluate utility of preclinical safety biomarkers for

monitoring organ safety in humans.

• To develop assays and devices for clinical application
• f safety biomarkers.
• To compile enough evidence to qualify safety

biomarkers for regulatory decision-making in clinical drug development in co-operation with the health authorities.

• To gain evidence for how safety markers may also be

used in the diagnosis of diseases.

Translational Safety Biomarkers Qualification Key Milestones and Deliverables

• Define clinical qualification processes for safety biomarker qualification

in clinical development with health authorities.

• Define the needs for new clinical biomarkers compared to current

standards and features/criteria to be met.

• Select biomarkers from different discovery exercises (e.g. PredTox, PSTC)

and develop assays / devices for human use.

• Establish baseline values and their variability in healthy subjects.
• Define and run protocols to measure the performance of these

biomarkers against current standards in clinical trials with expected drug- induced injuries and in patients with relevant diseases.

• Establish a common database to be able to build up on any new

dataset upcoming in the future and to share with health authorities.

• Qualify appropriate markers for regulatory decision making together with

health authorities.

The Innovative Medicines Initiative (IMI)

Improved Predictivity of Non-clinical Safety Evaluation

• Dr. Thomas Singer, D.A.B.T.

Global Head of Non-Clinical Safety

• F. Hoffmann-La Roche Ltd.

Research Focus

• Combined application of well-known toxicological

endpoints (histopathology, clinical chemistry) and novel technologies (toxicogenomics, metabonomics and proteomics) to evaluate hepatotoxicity and nephrotoxicity

• In depth data analysis within and across platforms and

studies

• Investigation of the underlying molecular mechanisms
• f toxicity and performance of confirmatory

mechanistic experiments

Project Plan

• Short-term in vivo animal studies, mainly in

rats but also selectively in non-rodent species, using

– ~10-15 drug candidates from companies and – ~10-15 reference compounds

• Biomarker discovery and non-clinical

qualification for regulatory decision making

Expectations from an Applicants Consortium

• Morphology /histopathology methods and expertise
• Transcriptomics technologies
• Latest metabonomics methodologies
• State-of-the-art capabilities in proteomics
• Capacities of mechanistic and confirmatory studies
• Information Technology and Data Evaluation

– Hosting and maintenance of the necessary IT infrastructure – Integrated data analysis

• Expertise in biological interpretation / integration of

results

• Expertise in education of scientists within Systems

Toxicology

• Representatives from the Regulatory Authorities

Pre-existing Experience and Rationale

• EU FP6 InnoMed Project – with PredTox Project

– Precurser for all IMI projects in terms of stakeholder collaboration

• InnoMed-PredTox to be accomplished by Jan-2009
• Output of value for pertinent topic/project
• Discovery and qualification of non-clinical safety

biomarkers is the first step in a multistage procedure to develop new safety markers for humans /patients

• Project outcome (markers) to feed into the

“Qualification of Translational Safety Biomarkers” project

The Innovative Medicines Initiative (IMI)

Priority Areas for Research to Strengthen the Monitoring of Benefit: Risk of Medicines Liz Swain Director of Medical Governance Operations and R&D Policy at GlaxoSmithKline

Background

• EMEA and European Commission are jointly

working to facilitate the availability of innovative medicines to patients

• Essential to have a thorough post-marketing

surveillance system of marketed products to ensure a positive benefit: risk balance

Background

• Pharmacovigilance tended to be a reactive

process focussing on spontaneous reporting

• Often insufficient to allow meaningful

assessment due to under-reporting and poor data quality

Post Post-

• marketing

marketing pharmacovigilance pharmacovigilance – – a challenging a challenging and and labour labour-

• intensive process

intensive process

• Reporting process is voluntary

Reporting process is voluntary… …difficult to assess whether there are difficult to assess whether there are excess reports of a particular adverse event excess reports of a particular adverse event -

• no denominator or

no denominator or control group, signal vs. noise. control group, signal vs. noise.

• Traditionally focused on individual cases

Traditionally focused on individual cases -

• no systems

no systems-

• based tools for

based tools for signal detection/evaluation or quantitative analysis signal detection/evaluation or quantitative analysis

• Nonetheless this is important safety information which is used t

Nonetheless this is important safety information which is used to make

• make

decisions decisions

The Importance of Proactive Pharmacovigilance

Observations of Current Situation by IMI Pharmacovigilance Stakeholder Group

• A wealth of epidemiological data on drug exposure

and outcomes is available in the EU, but

– No central repository of such data – Different data sources do not communicate – Data cannot be combined

• Systems and networks for pharmacovigilance are used

for regulation, not for research

• Methods of pharmacovigilance have remained

unchanged for two decades

• Risk minimisation methods are not yet available for

testing

• Effectiveness of risk communication is put into question

Proposals from IMI Pharmacovigilance stakeholder group

• Optimisation of data resources and strengthening
• f evidence base in pharmacovigilance
• Development and strengthening of

methodologies and networks of pharmacovigilance

• Development of novel methods of risk prediction

and benefit : risk assessment

• Training and education of Health Care

Professionals and patients (see training and education call)

What are we aiming to improve?

• Goal is to increase confidence in the post-

marketing monitoring of benefit: risk of EU medicinal products , ultimately facilitating an earlier access of novel medicines for the benefit of EU patients

• Scope is to optimise data resources and

strengthen the evidence base through development of methodologies and networks in the EU

Opportunities for Research to Strengthen the Monitoring of Benefit:Risk of Medicines

• Establish new methods of pharmacovigilance data

collection

• Evaluate methods and develop operational

definitions for

• signal detection and evaluation in spontaneous

reports databases, and

• population-based epidemiologic data sources
• Establish methods for graphical expression and

comparison of the benefit : risk profile of medicinal products

• Investigate and develop standards and processes

for interoperability of European epidemiology data sources

Research = Patient Benefit

The Innovative Medicines Initiative (IMI)

http://imi.europa.eu www.imi-europe.org

The Innovative Medicines Initiative (IMI)

IMI Efficacy Calls

The Innovative Medicines Initiative (IMI)

April 30th , 2008

Diabetes Calls: Islet cell research Surrogate markers for vascular endpoints

Veikko Koivisto, MD, PhD Eli Lilly & Co

Diabetes Call Topics

• Islet Cell Research: Improving Beta Cell

Function and Identification of Biomarkers for Treatment Monitoring in Diabetes

• Surrogate Markers for Vascular Endpoints:

Surrogate Markers for Micro- and Macrovascular Hard Endpoints to Shorten Clinical Trials in Diabetes

Islet Cell Research I

• Focus

– Beta cell dynamics in vitro and in vivo – Cross talk of beta cells with other cell types in islets and with other tissues or organs

• EFPIA Participants (n=10)
• Astra Zeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novartis,

Novo Nordisk, Roche, Sanofi Aventis, Servier, Solvay

Islet Cell Research II

• Beta cell dynamics in vitro and in vivo

– Origin, source and function of novel beta cells – Conditions for beta cell proliferation and differentiation from precursor cells – Genetic and genomic studies for identification of biomarkers – Beta cell apoptosis: its mechanisms, prevention, measurement

• Novel technologies, tools, approaches

– Novel animal models or in silico tools – Novel biomarkers for beta cell function and islet regeneration – Non-invasive technologies for monitoring beta cell mass

• Imaging, nanotechnologies, biomarkers

Islet Cell Research III

• Cross talk with beta cells and other cell types

– Abnormalities with alpha cell function, alpha/beta cell ratio – Interaction between islet cells and gastrointestinal tract

• Key deliverables

– Generation of tools – Identification and validation of biomarkers and novel mechanism and targets for diagnosis and therapy – Knowledge on

• mechanism of beta cell loss in type 1 and type 2

diabetes

• beta cell proliferation and differentiation

Surrogate Markers for Vascular Endpoints I

• Focus

– To find ways to shorten clinical trials on hard vascular endpoints in diabetes – Retrospective: Analyse data in already performed or ongoing clinical trials – Prospective approach: Perform novel trials to search and validate the surrogate markers

• EFPIA Participants (n=8)
• Boehringer Ingelheim, Eli Lilly, Novartis, Novo

Nordisk, Pierre Fabre, Roche, Servier, Solvay

Surrogate Markers for Vascular Endpoints II

• Analysing data in already performed studies

– Genotype, phenotype, biomarkers, outcomes – Surrogate markers for micro- and macrovascular endpoints

• Novel prospective studies

– Preclinical biomarkers and surrogate endpoints in animal studies – Develop in silico tools to reduce animal experiments – Validate surrogate markers obtained from earlier studies – Perform novel biomarker and genomic analysis to be validated by hard endpoints

Surrogate Markers for Vascular Endpoints III

• Key deliverables

– Validated, industry-relevant, clinically meaningful and agency -acceptable biomarkers – Validated genotypes of type 1 and type 2 diabetic patients, who are prone to develop micro- or macrovascular complications – Novel assays (biochemical, imaging etc) – Novel in silico models, which reduce the need

• f animal studies

– New tools for the development of therapies – A model for clinical research collaboration between key stakeholders

THANK YOU VERY MUCH

The Innovative Medicines Initiative (IMI)

Brain disorders Tine Bryan Stensbøl

Head of Discovery Pharmacology Research Division, Lundbeck

Bruxelles , April 30th 2008

General considerations for Psychiatric disorders, Neurodegeneration and Pain

• Issues, Needs, Background

– Management of these diseases are unsatisfactory – Pathophysiological processes and etiologic factors these diseases remain elusive – As a consequence, safe therapies that effectively relieve core symptoms or delay disease progression are a major challenge.

• Scope

– Gain greater insight into pathways and mechanisms underlying Psychiatrc disorders, Neurodegenerative disorders and Pain. – Develop translatable efficacy, pharmacodynamic and pharmacokinetic pain measures and models in animals and humans – Establish and validate human models – Develop robust markers for patient stratification

Psychiatric disorders

Issues, Needs, Background & Scope

• Issues and Background

– Pathophysiological processes and etiologic factors within psychiatric disorders remain elusive. – As a consequence, safe therapies that effectively relieve core symptoms

• r delay disease progression are a major challenge.
• Needs

– Systematic research into human disease biology – Biomarker identification linked to disease pathophysiology – Translation of sensitive markers into preclinical models

• Scope

– Development of platforms that translate efficacy of novel therapeutic approaches into measures for clinical assessment including experimental medicines paradigm , such as

• Blood/CSF markers
• Neuroimaging
• Electrophysiological read-outs

Goals & Related Project Plans

• Improving Understanding of Disease Biology & Treatment Effects

– Transcription patterns - correlation between human blood and

• brain. Advancement of the disease biology understanding.

– Correlation of blood markers (metabolites, gene transcription) with disease states and treatment response – Identify marker profiles that predict treatment response

• Improving animal models

– Improved understanding of disease biology and associated markers leading to improved animal models – Focus on read-outs relevant as endpoints in clinical studies – PK/PD modelling – confirmation of pharmacology in humans vs animals

• Improving dose selection

– Establish tools to obtain clinically relevant target occupancy – support dose selection and relate to relevant read-outs e.g., functional neuroimaging

Deliverables 1

• Identify relevant markers to segment patient

populations

– Identify blood markers related to distinct phenotypes, including intermediate phenotypes: used for early signs

• f clinical efficacy

– Identify blood markers that predict treatment response: to enrich study populations – Validate pharmacodynamic markers to support regulatory submissions – Use transcription markers to guide genotyping. – Use markers to identify novel treatment targets – Link transcription patterns to phenotype – Experimental medicine models

Deliverables 2

• Improve animal models

– Establish animal models that share marker changes identified in

• humans. Focus on ‘translatable’ read-outs, e.g. blood markers,

neuroimaging, EPs, EEG – Develop models of PK/PD relationships on pharmacodynamic markers

• Improve dose selection

– Establish functional neuroimaging read-outs that correlate with target occupancy and clinical efficacy to facilitate dose selection – Establish preclinical in vivo validation of clinical neuroimaging read-outs

Participants EFPIA

– AstraZeneca – Eli Lilly – GSK – Johnson & Johnson – Lundbeck – Novartis – Orion Pharma – Pfizer – Pierre Fabre – Roche – Servier – Solvay – Wyeth

EFPIA contribution

– All companies are committed to deliver in-kind contributions – Level of in-kind contributions remains to be determined, depending on proposals

• ‘In kind’ contributions

– ‘Omics platform’ and neuroimaging expertise – Translatable’ animal models (e.g. transgenic animals, preclinical models) – Markers/samples/patients from ongoing EFPIA-company sponsored pre-clinical and clinical studies – Mathematical modelling/handling of data – Development of PET ligands – Project management: Close interaction with public partners to ensure effective management and systematic and co-ordinated approach to ensure goal completion

Neurodegeneration

The challenge to delivering successful medicines in the field of Neurodegeneration

• Issues, Needs, Background

– Clinical outcome studies in Neurodegenerative disorders are notoriously long and expensive – Positive proof of efficacy or futility is often not identified until late in development

• Scope

– to validate biomarkers, novel pharmacodynamic models and develop more predictive animal models

Key areas addressed by research proposal

• Healthy Volunteer/Pharmacodynamic model development

– Novel approaches to well described models : e.g. scopolamine challenge, sleep deprivation, diurnal vigilance – Innovative model design/validation to deliver the next generation of HVT models

• Pharmacodynamic marker development

– identify pharmacodynamic markers acutely altered by drug activity (i.e within 4-6 weeks) – Exploit pharmacological tools available from EFPIA partners to identify :

• those markers with utility across a variety of different therapeutic classes, or

across indications, such as biochemical, functional or imaging markers for atrophy, brain degeneration or reduced activity in defined brain regions

• Markers with utility to support translation from pre-clinical models to HVT

(young and elderly) to patients

• Pre-clinical model development

– Develop pre-clinical models to support early drug screening by capitalising on the consortium’s pre-clinical and clinical expertise to develop pre-clinical models in parallel to the clinic, using fully translatable endpoints.

• Healthy Volunteer/Pharmacodynamic model development

– Identification of cognitive impairment models predictive of effective dose range and eventual clinical efficacy – Academic and industrial agreement on predictive value to disease states

• Pharmacodynamic marker development

– Identification of markers validated and widely accepted as being suitable

• for predicting pharmacologically active exposure range within 4-6 weeks

dosing

• For use across pre-clinical species, HVT and/or patient studies
• Pre-clinical model development

– Identification of animal models using fully translatable endpoints and scientifically proven utility in the translation of efficacy from bench to bedside Delivery of academically and industrially validated models and markers to revolutionise future drug development.

The primary aims and impact on both industrial practices and academia

Deliverables Neurodegenerative disorders

• Identification of and pharmacological validation of parallel HVT and

preclinical pharmacodynamic models to estbalish effective exposure ranges and support poc

– Characterisation of HVT and preclinical PD models (e.g. sleep deprivation) using clinically validated agents – Identify PD endpoints most sensitive to pharmacological intervention in HVT and preclinical models. – Identification of model with highest predictive capacity

• Identification and pharmacological validation of novel in vivo

animal models

– Development, validation and refinement of pre-clinical models using fully translatable endpoints and increased predictive capacity. – Identification and validation of PD markers to support preclinical and early clinical assessment in HVT/disease populations and that translate from bedside to bench

EFPIA participants

• AstraZeneca
• Boehringer-Ingelheim
• GSK
• Johnson & Johnson
• Eli Lilly
• Lundbeck
• Merck Serono
• Novartis
• Pfizer
• Pierre Fabre
• Roche
• Servier
• Solvay
• UCB

EFPIA contribution

• Estimation of “in kind” contributions from EFPIA members

– Supply of pharmacological tools/molecules with broad ranging therapeutic targets – Access to placebo data (pre-clinical/clinical) – Access to Tg mice/in vivo models of disease – Increase sample size via access to samples/patients from

• ngoing EFPIA sponsored pre-clinical (rodent and primate)

and clinical studies – Access to ‘omics platforms’ and imaging expertise – Increase sample size via access to data/subjects from experimental medicine studies exploring HVT models – Access to biomarkers identified in EFPIA sponsored studies – Close interaction with public partners to ensure effective management and coordination of work to deliver key

• bjectives

Pain Research

What are we trying to solve?

• Issues, Needs, Background:

– Examination, diagnosis and treatment of chronic/neuropathic pain according to anatomical pain site or underlying disease is of limited help to patients and their pain. – Clinical studies generally designed in this manner. – Rational, mechanism-based approaches to C/NPP are needed

• to increase treatment efficacy beyond 50 % pain reduction in

about 50 % of patients

• to improve side-effect profiles.
• Scope:

– Gain greater insight into pathways and mechanisms mediating different kinds of pain – Develop translatable efficacy, pharmacodynamic and pharmacokinetic pain measures and models in animals and humans – Establish and validate human pain models – Develop robust markers for patient stratification and quantitative pain assessment

What are we expecting and going to do?

Project plan outline:

• 1. Identify mechanisms involved in generating and sustaining pain:
• 2. Develop more predictive preclinical animal models:
• 3. Develop models and markers to translate pain outcomes and pharmacology

between animals and humans:

• 4. Objective and quantitative assessments of pain for use in clinical trials:
• 5. Analyze abuse potential:

What are we expecting and going to do?

Project plan outline:

• 1. Identify mechanisms involved in generating and sustaining pain:
• Peripheral and central sensitisation
• Modulation of inflammatory mediators, neuronal activity and neuroplasticity
• 2. Develop more predictive preclinical animal models:
• Mechanisms and end-points translatable between animals and man

(linked to clinical electrophysiology and brain imaging)

• Towards pain-free models of pain
• 3. Develop models and markers to translate pain outcomes and pharmacology

between animals and humans:

• Mechanism-based human models of pain
• Comparison of preclinical and clinical data-bases obtained with established analgesics, negative

controls and NCEs

• 4. Objective and quantitative assessments of pain for use in clinical trials:
• Quantitative sensory testing (QST)
• Functional or ‘wet’ biomarkers that correlate with clinical efficacy
• fMRI, EEG/evoked potentials, MEG or other quantitative physiological responses
• Factors underlying the placebo response in analgesic drug trials
• 5. Analyze abuse potential:
• Imaging technologies: validated cerebral profiles of the positively reinforcing, psychostimulants

What are we expecting and going to do? Deliverables 1

• 1. Mechanisms involved in generating and sustaining pain:

1.1. Peripheral sensitisation, central sensitisation and neuroplasticity 1.2. From bedside to bench -Translation back to animal models 1.3. Methods and techniques to analyse the placebo response in clinical trials on pain

• 2. Preclinical animal model development:

2.1. Validate novel animal models: mechanism and origin specific, RA, HIV, cancer, diabetic 2.2. Objective, quantitative and clinically translatable pain measures: 2.3. Development of pain-free animal models of pain (3Rs) (imaging, molecular profiling, collateral behavioural markers) 2.4. Eliminating user bias in experimental pain assessment.

What are we expecting and going to do? Deliverables 2

• 3. Develop models and markers to translate pain outcome and pharmacology

between animals and humans:

3.1. Combined use of brain electrophysiology (EEG, MEG) imaging (fMRI, MRS) and molecular profiling (genetics, transcriptomics, proteomics or metabonomics) 3.2. Translatable preclinical/human experimental pain models, to be used for selection of biomarkers and decision-making concerning patient stratification.

• 4. Objective and quantitative assessments of pain for use in clinical trials:

4.1. Refine and extend experimental clinical methods of objectively measuring pain 4.2. Investigate placebo effects in pain clinical trials by detailed review of placebo data provided by consortium members.

What are we expecting and going to do? Deliverables 3

• 5. Delineate phenotypes of chronic pain patients:

5.1. Make different methodologies converge (e. g., genetic linkage, QST, novel methods) 5.2. Conduct small-scale, stratified clinical studies, which can deliver reliable early efficacy signals.

• 6. Brain imaging for objective evaluation of the abuse potential of novel

analgesics.

• AstraZeneca
• Boehringer-Ingelheim
• Eli Lilly
• Esteve
• GSK
• Merck
• Orion Pharma
• Pfizer
• Pierre Fabre
• Sanofi Aventis
• UCB
• Wyeth

EFPIA participants

Pre-clinical and clinical scientific expertise and the sharing of pre-clinical models, human experimental pain data and clinical trial data on non-proprietary compounds.

• Clinical trial expertise
• Pain clinical trial placebo data
• Clinical supply of marketed products
• Tool molecules (clinical and pre-clinical)
• Clinical and pre-clinical brain imaging facilities
• Blood/CSF/biochemical biomarkers
• Transgenic mouse strains/models
• Animal models of chronic/neuropathic pain
• Behavioural measures of chronic/neuropathic pain

EFPIA contribution

Expectations from public consortium

• general
• Expected contribution from academic groups and

SMEs

– Innovative approaches for patient characterization, including intermediate phenotypes, that cross current diagnostic

• boundaries. Includes established infrastructure to recruit subjects

– Disease biology understanding – Availability of blood samples from well-phenotyped subjects, that are suitable for omics technology – Technology platforms (animal models, imaging technologies) – Access to animal models that mimic aspects of human disease – Innovative approaches to the challenge of pharmacodynamic model/marker development – The ability to combine expertise to allow an integrated approach to model/marker development e.g. combining clinical assessment with imaging, EEG/MEG and/or biochemical/genetic assessment – The ability to conduct parallel pre-clinical and clinical studies to allow maximum understanding of forward and back translation - Consortia should have both clinical and preclinical groups

What is expected from the public Consortium?

• Seek synergies with other related global initiatives:

– ADNI – Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium (www.biomarkersconsortium.org.) – InnoMed, AdNeuroMed (www.Innomed.addneuromed.com) – US Biomarker consortium – CNS Metabolomics consortium – P1 Vital

The Innovative Medicines Initiative (IMI)

2008 Respiratory Calls:

COPD Patient Reported Outcomes Understanding Severe Asthma

Chris Compton MD

Pfizer on behalf of the EFPIA Respiratory Group

Strategic Research Agenda (SRA): COPD, Asthma, Rhinitis

• SRA identified three priority respiratory diseases based on

medical need: COPD, Asthma and Rhinitis

• For each disease key bottlenecks fall into three main areas:

– Disease understanding: Epidemiology, diagnosis, assessment of severity, phenotyping, biochemical and genomic markers – Translational models: Identification and validation of new preclinical and clinical models to facilitate translational research – Measuring outcomes: Selection and validation of Patient Reported Outcome (PRO) tools that can be used to generate data to evaluate the effects of pharmacological interventions from a patients perspective. Such data can inform regulatory and payer evaluations of treatment benefit.

• Objective is to build a European Network or “Centre of

Excellence” for each disease area through the life of IMI, starting with 2008 calls

– 2008 calls will be focused on ‘Disease Understanding’ for Severe Asthma and ‘Measuring Outcomes’ for COPD – Calls for 2009 and beyond will speak to other bottlenecks for the three diseases

What is COPD?

• A disease with distinct pathologies

– Bronchitis – Emphysema – Small airway remodeling – Vascular remodeling – Systemic disease – Infection

• Mortality still increasing
• Causes significant disability and use
• f health-care reources, resulting

from patients experience of daily symptoms and exacerbations

• High prevalence

but under-diagnosed

– The Fourth most common Chronic Disease

• Preventable disease

– Caused by smoking!!!!!

Stang, 2000

Estimated total COPD ~ 16 million in EU Diagnosed COPD ~ 2.4 - 7 million in EU

Tunel PCNA

Lung Alveoli in Emphysema

Extensive apoptosis and cell division

2008 COPD Patient Reported Outcomes (PRO) call: Background

• Evaluation of efficacy of new therapies has relied on the

demonstration of reduction of airflow obstruction.

– This does not capture the potential benefits that the patients experiences – Capturing the COPD patients’ experience of the disease and effects of treatment is key to evaluating treatments for COPD – European Regulatory guidelines recommend the use of symptom endpoints, in addition to lung function measurements, for evaluating treatments for COPD

• A PRO is any report coming directly from patients, without

interpretation by physicians or others, about how they function or feel in relation to a health condition and its

• therapy. PRO Measurement tools should be generated

with adequate patient input.

Important aspects to measure when evaluating outcomes of treatments for COPD.

• A patient with COPD experiences a variety of symptoms

including dyspnoea (shortness of breath).

– Symptoms of COPD restrict patients’ ability to perform daily activity and also results in psychological consequences resulting in significant impairments to overall health status.

• COPD patients also experience acute worsening of their

symptoms- exacerbations- that often require a change in their treatment, sometimes even requiring hospitalization.

• There is a need for scientifically developed and validated

PRO measures that capture symptoms, exacerbations and their impact on patients

– Enable solid evidence on outcomes that reflect the patients’ perspective on product label claims.

COPD call: What are we trying to solve?

• Objectives

– Understanding of the patients’ experience of COPD to inform the strategy to measure outcomes that are relevant to patients for assessing treatment benefit – Selection and/or Development of measures with good measurement properties that capture the COPD patients’ experience of the disease and effects of treatment

• To inform the definition of exacerbation
• Understand day-to-day experience of symptoms
• Evaluate impact of these symptoms
• Scope

– To build consensus on the measurement strategy, especially PRO tools, by working with the key consumers of the information on treatment benefit:

• Clinical practitioners, academic clinical & health
• utcomes researchers, patients and payers

COPD call: What are we expecting and going to do?

Deliverables

• A measurement strategy that includes

specific PRO tools:

– Developed using robust psychometric methods

• With input from and review by the major customer

groups

– Validated for use in treatment evaluations across Europe that can link to global efforts

• Using appropriate prospective studies

– Developed or adapted for capturing data using electronic data capture (EDC) devices for daily recording at home

COPD call: What are we expecting and going to do?

Project plan outline

• Planned in two phases :

– Phase A: Develop a framework to understand the Patients experience of COPD, especially in the European context, to inform strategies to measure outcomes meaningful to patients in global clinical trials – Phase B: Develop/select and validate PRO measurement tools, to use in clinical trials evaluating treatments for the disease

COPD call: What is expected from a public Consortium?

A Consortium or ‘Centre of Excellence’

• To develop a measurement strategy to evaluate the benefits of

COPD treatment from a patients’ point of view

• With contributions from the key customers and ‘Subject Matter

Experts’. For example…

• University
• Clinical centres
• SME researchers
• Patient groups
• EMEA
• Payers
• Health Technology Assessment agencies
• Agencies that make decisions about reimbursement

– It is important to link to and build on existing ‘Initiatives for the measurement of PROs in COPD’ to avoid redundancies

Asthma an illness that afflicts all ages

1. Mild and moderate disease

– Controlled for most patients

2. The most successful classes of drugs:

– 35 years old

3. The severe asthmatics carry most of the costs of care and are poorly served

2%

8% 20% 30% 40% 24% 30% 33% 10% 3%

Degree of control Total Cost

Uncontrolled

• n treatment

Controlled

• n treatment

Rarely symptomatic

Understanding Severe Asthma Call: Background

• There is high unmet need for more effective,

convenient and safe therapies, particularly for patients with moderately severe and severe disease.

• 10% of asthmatics with the most severe disease

account for up to 50% of the total costs of asthma care.

• Disease understanding including epidemiology,

diagnosis, assessment of severity, phenotyping, biochemical and genomic markers of severe asthma is key

Understanding Severe Asthma call: What are we trying to solve?

• Issues, Needs, Background

– A. Understanding natural history of severe asthma and disease mechanisms presents considerable challenges in the setting of disease heterogeneity, including its frequent co-morbidities – B There is a need for further development of internationally agreed diagnostic criteria for mechanistic and therapeutic trials, – C Need for research into disease mechanisms to provide for true- disease modifying therapeutic opportunities, biochemical and genomic biomarkers to identify patient characteristics associated with different phenotypes – D There are groups working independently to address some of these questions. Need for standardised approach

• Scope

– The asthma call for 2008 is to build an EU Severe Asthma network focused on disease understanding.

Understanding Severe Asthma call: What are we expecting and going to do?

• Deliverables

–

EU and globally agreed (ERS/ ATS as well as regulatory agencies) diagnostic criteria for severe asthma – Identification as well as subsequent validation of novel targets for pharmacological intervention and biomarkers to assess pharmacological response or predict effects on clinical outcomes – Understanding of aetiology and pathogenesis of asthma exacerbations as mechanism to identify new targets and therapeutic approaches – Accurate targeting of an intervention to a particular, well-defined patient sub-population. – Capability to develop translational models for appropriate prediction of clinical relevance through preclinical modelling. – Access to defined patients which will facilitate enrolment and study of patients for clinical trials by academic and pharmaceutical research.

• Project plan outline

– 1 Consensus meeting – 2 Form a scientific committee – 3 Define common protocol for patient identification and assessment together with a common database or prospective registry – 4 Undertake cross sectional and longitudinal study

Understanding Severe Asthma call: What is expected from a public Consortium?

A Consortium or ‘Centre of Excellence’

• With contributions from the key customers and ‘Subject

Matter Experts’. For example…

• University
• Clinical centres
• SME researchers
• Patient groups
• EMEA
• CRO
• Other global initiatives to be followed/contacted to

avoid redundancies and build on synergies

The utility of a properly constructed and maintained patient cohort

Define disease Recruit cohort Newly defined cohort

Innovative Clinical measurements New model development

Longitudi nal study

New clinical study design Optimal dosing ideal PK/PD and high therapeutic index Optimal clinical measures of efficacy

The Innovative Medicines Initiative (IMI)

http://imi.europa.eu www.imi-europe.org