Transcript Translational Approaches To T1DM
From IMI to IMI2 Hugh Laverty
Senior Scientific Project Manager
Vilnius, 11 th September 2014
The way in which pharmaceutical companies develop new medicines is changing
Regulators Rising R&D cost Patent cliff
Pharma
EU Pricing HC Reform Generics Declining R&D productivity
New approaches needed
“Deciphering the complexity of human diseases and finding safe, cost-effective solutions that help people live healthier lives requires
collaboration across scientific and medical communities throughout the health care ecosystem
.
Indeed, we must acknowledge that
no single institution, company, university, country, or government has a monopoly on innovation
.”
Innovative Medicines Initiative:
Joining forces in the healthcare sector
The biggest public/private partnership in Life
Science aiming to: • Make drug R&D processes in Europe more
innovative
and
efficient
• • Enhance Europe’s
competitiveness
Address key
societal challenges Features:
• • 1:1 funding, joint decision making All EU funds go to SMEs, academia, patient organisations and regulatory agencies • Large pharmaceutical industry, represented by EFPIA, contributes in-kind
How it works
Step 1 Topic Definition & Launch EFPIA IMI SMEs Academic research teams Step 2 Hospitals EoI Submission Applicant Consortia Step 3 Full Project Proposal Submission 1 st ranked EoI + EFPA Regulatory authorities Patients’ organisations Step 4 Governing Board approval IMI Step 5 Signatures & project kick-off The Consortium Call Launch 18 weeks 1 st ranked EoI Selection 9 weeks GB approval of 1 st ranked FPP negotiations start 6 weeks Signatures & project kick-off
The IMI community Calls 1-8 46 projects
410 EFPIA teams 714 academic & research teams 135 SMEs
> 6000 researchers
23 patient org.
14 regulators 61%
of projects reported some form of
PATIENT INVOLVEMENT REGULATORS
ON BOARD OF
12
PROJECTS
50%
of projects have
REGULATORY AUTHORITIES
representatives in Scientific Advisory Boards
The IMI portfolio
Calls 1-8 participations per country
IMI projects
IMI scientific output
350 300 250 200 150 100 50 0
708
PUBLICATIONS
3709
CITATIONS
2.04
CITATION IMPACT
19%
HIGHLY CITED
Number of publications per year 2009 2010 2011 2012 2013
Making a difference
Project IMIDIA DDMORE eTRIKS EUROPAIN
Implementation of project results inside industry
Area
diabetes knowledge management knowledge management
Results description The human beta cell line EndoC BetaH1 has been validated by Endocells and 3 pharma partners confirming their initial insulin secretion capacity.
These cells have been
successfully transferred as a research tool for drug discovery to industrial partners.
Several drug/disease models identified by DDMORE are
further developed inside the industry.
adopted or
Adoption of the eTRIKS results ,
TransMART system deployments in 5 pharmaceutical companies.
Chronic pain
Preclinical model of spontaneous pain in rodents has been developed, standardized, validated, and is already
used for internal decision making in the drug development process
.
The ultraviolet B (UVB) pain model has also started to be
used for in house R&D
.
Impact on regulatory framework
Project PROactive EU-AIMS eTOX MARCAR Safe-T DDMORE Area
COPD autism drug safety cancer drug safety knowledge management
Results description
Qualification Advice completed
at the EMA Started EMA formal scientific advice procedure for
biomarkers in ASD qualification of 5
Provided an update on the eTOX database and the prediction system to the CHMP Safety Working Party (SWP) at EMA.
Scientific Advice Procedure was initiated
.
Has developed new biomarkers, technologies, and alternative test systems that help explain or predict animal and/or human carcinogenic pathways and mechanisms for non-genotoxic carcinogenesis. This will provide enhanced scientific rationale for Carcinogenicity Assessment Document (CAD) submissions, with
potential impact for ICH S1 carcinogenicity testing guideline revisions
.
Developed and now
progressed towards an aligned EMA/FDA qualification
a set of novel safety biomarkers for drug-induced kidney, liver, and vascular injury.
In May 2012 an advisory meeting with EMA and FDA representatives was held.
Through a Modelling Review Group , DDMoRe is in regular contact with both the EMA and FDA regarding the qualification of the content of the project’s Model Library.
SME participation in IMI projects (up to 8
th
Call)
Total IMI commitment Total received by SMEs % SME Total IMI participations Total SME participations % SME
€ 723 million € 133 million 18.4% 886 135 15%
SME success stories
SME involved in SAFE-T project “ Thanks to IMI our company went from
6 to 50 employees.
Now we are ready to go to further expand.” SME involved in IMIDIA project – “1 st product released to the market in 2013 –
the first cell line product
, 2 nd
IMI was instrumental in validation of
product release planned this year, 3 rd diagnostic product in development.
In preparation :
a new patent filing
to protect technologies for the creation of third generation human beta cell lines.
SME involved in PharmaCog project “We are developing a blood panel for AD for diagnosis, stratification and companion diagnostics in AD.
The Panel was tested on 300 patients in IMI project
” SME involved in eTOX project “We have developed in silico models for predicting toxicity, which were validated by pharmas in eTOX. Now
we have signed a contract with one of the companies to use our models in house
.”
Promoting patient involvement
IMI makes efforts to enhance patient centric approach − Patient dedicated workshops − Involving patients at all levels − Providing forum for discussion
IMI best practice examples:
EUPATI U-BIOPRED PROactive
For patient-centric R&D more trained patients are needed
Public Committees Competent authorities
Trial protocol design, informed consent, ethical review, marketing authorization, value assessment, health policy
Policy makers Research Ethics HTA agencies & committees Driving force Co-researcher Reviewer Advisor Info provider Research subject Clinical Research
Paradigm shift in empowering patients on medicines R&D
Key European initiative to provide objective,
credible, correct and up-to-date public knowledge about medical research
Will build competencies & expert capacity among patients & public Will facilitate patient involvement in R&D to collaborate in academic research, industry research, authorities and ethics committees
Collaboration
Key collaborative activity areas:
Diabetes, CNS disorders, Tuberculosis, Patient Reported Outcomes, Cancer, Preclinical Safety and Education & Training. IMI signed horizontal agreements with: Critical Path, Juvenile Diabetes Research Foundation as well as with Clinical Data Interchange Standards Consortium.
The measures of success
SUCCESS
New models developed & published Setting new standards In house implementation by industry Impact on regulatory guidelines
Better Science = Better Decisions
IMI’s drug discovery platforms
European Lead Factory Focus: identification of new hits European Lead Factory
‘Qualified’ hit
ELF Budget:
€92.0m EFPIA in-kind
€80.0m
IMI JU
www.europeanleadfactory.eu
Target screening Hit-to-lead Lead-to candidate Preclinical Phase I Phase II Phase III ND4BB Drug Discovery Platform
Lead
nd4bb-enable.eu
Clinical Candidate
ENABLE Focus: to move promising hits into early clinical development
Phase 1 ready
ENABLE Budget:
€26.0m EFPIA in-kind
€58.9m
IMI JU
Towards IMI2
The Evolution of IMI:
From bottlenecks in industry – to bottlenecks in Industry and Society Make Drug R&D processes in Europe more efficient and effective and enhance Europe
’
s competitiveness in the Pharma sector Idea generation Basic research and non-clinical testing Human testing Regulatory Approval HTA and Pharmacovigi lance Daily Medical practice Primary focus of early IMI calls 2007 SRA Shift to also addressing challenges in in society and healthcare 2011 SRA IMI 2 includes real life medical practice 2013 SRA
The Vision for IMI2 – The right prevention and treatment for the right patient at the right time
Biologically heterogeneous patient population effective not effective Adverse events Trial and Error vs Dx Test e.g. biomarker effective A not effective adverse events Information based treatment decisions B C
Graphic adapted from C. Carini, C. Fratazzi, Eur. Pharm. Rev. 2008, 2, 39-45
Science is driving advances in diagnosis: breast cancer is actually 10 different diseases
Thursday April 19 2012
“A landmark study has reclassified the country’s most common cancer in breakthrough research that could revolutionise the way we treat breast tumours… scientists found breast cancer could be classified into 10 different broad types according to their common genetic features.” http://www.nhs.uk/news/2012/04april/Pages/breast-cancer-genetic-diversity-mapped.aspx
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Objectives of IMI2 – what the Regulation says
• • • • • • increase the success rate in clinical trials where possible, reduce the time to reach clinical proof of concept in medicine development develop new therapies for diseases for which there is a high unmet need and limited market incentives develop diagnostic and treatment biomarkers for diseases clearly linked to clinical relevance and approved by regulators; reduce the failure rate of vaccine candidates in phase III clinical trials through new biomarkers for initial efficacy and safety checks; provide support for the development of tools, standards and approaches to assess efficacy, safety and quality of regulated health products.
The premises
• Alignment with
Horizon 2020
objectives of the Health challenge • Addressing healthcare priorities identified by the WHO 2013 report on priority medicines for Europe and the world • Strategic Research Agenda aimed at progressing the vision of personalised medicines, for both prevention and treatment • Collaboration across sectors to harness all knowledge and technologies which can contribute to IMI2 vision - diagnostics, imaging, IT, medical devices, …
Table of Contents
1. Introduction and Background .................................................................................................... 9 1.1. 1.2. The Strategic Research Agenda (SRA) ................................................................................. 9 The aim and vision of IMI2 – The right prevention and treatment, to the right patients at 1.3. the right time .............................................................................................................. 10 Building on the strengths of Europe .................................................................................. 11
societal challenge reflected in the IMI2 SRA
2.2. Challenges facing the healthcare ecosystem of today ...................................................... 15 The role of Research & Development in addressing healthcare challenges ..................... 16 2.3. Regulatory, health technology assessment and healthcare delivery challenges .............. 18 3.Research Objectives of IMI2 ..................................................................................................... 19 12 10 8 6 4 2 0
WHO report: Percentage of DALYs for top 20 high burden diseases and conditions
3.1. Four major axes of research .............................................................................................. 19 3.1.1. Axis 1: Target validation and biomarker research (efficacy and safety) ........................... 19 3.1.2. Axis 2: Adoption of innovative clinical trial paradigms ..................................................... 21 3.1.3. Axis 3: Innovative Medicines ............................................................................................. 23 3.1.4. Axis 4 : Patient tailored adherence programmes .............................................................. 24 4.Enabling Technologies ............................................................................................................. 28 4.1. Excellence in Data Management ................................................................................ 28 5.Implementation strategies ....................................................................................................... 29
Therapeutic Areas in IMI2 SRA
(no priority order) 6.European Health Priorities to be addressed by IMI2 ................................................................. 32 World 6.1. Antimicrobial resistance .................................................................................................... 32 6.2. Osteoarthritis .................................................................................................................... 34 6.3. 6.4. 6.5. 6.6. 6.7. 6.8. Cardiovascular diseases ..................................................................................................... 37 Diabetes ............................................................................................................................. 39 Neurodegenerative diseases ............................................................................................. 41 Psychiatric diseases ........................................................................................................... 44 Respiratory diseases .......................................................................................................... 46 Autoimmune diseases ....................................................................................................... 48 6.9. Ageing-associated diseases ............................................................................................... 50 6.10. Oncology ............................................................................................................................ 52 6.11. Rare/Orphan Diseases ....................................................................................................... 55 6.12. Vaccines ............................................................................................................................. 58 7.Translating research to tangible benefits for European and Global Healthcare infrastructures ... 61 8.Impact of IMI2 on the use of animals in research and development .......................................... 64
Reference List
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IMI2: Major Axes of Research
Reclassification of disease by molecular means Target Identification and validation(human biology) Determinants of drug /vaccine Safety and efficacy Innovative drug delivery methodologies Biomarker identification/validation (precision medicine) Target & Biomarker Identification (safety & efficacy) Innovative Medicines Innovative clinical trial paradigms
European Health Priorities
Patient tailored adherence programmes Manufacturing for personalised medicines Discovery and Development of novel preventative and therapeutic agents Innovative methodologies to evaluate treatment effect Adoption of innovative clinical trial designs Benefit/Risk Assessment Healthcare delivery: focus on the treatment programmes not just the medicine Innovative adherence programmes
Drive change in delivery of medical practice
Strategic Research Agenda
Comprehensive framework for a 10-year programme Prepared with input from 80+ organisations (internet and targeted) Project ideas from industry and third parties will be screened against it http://goo.gl/jqMP9g
IMI2 - Broad participation to be able to set ambitious goals
IMI is evolving, with a stronger focus on the needs of patients and society and with simpler rules and procedures Evolution in scientific focus
• Stronger focus on needs of patients and society, including unmet needs • Increased emphasis on improving patient access to innovative medicines (in addition to medicines development) • Focus on personalised medicine (
the right treatment for the right patient at the right time
)
IMI2 - Broad Participation to achieve ambitious goals:
Bigger budget: 3,45 Billion Euro, equally shared by EU and industry Not limited to EFPIA members: open for other industries / companies, which can contribute to the PPP goals (Healthcare IT, medical devices,…) giving them the opportunity to establish their own projects The principle of large companies providing an inkind contribution matched by IMI funding for public beneficiaries will be retained.
IMI2 - Broad Participation to achieve ambitious goals:
Specified Budget: 225 million Euros reserved for non-EFPIA led projects (to be matched by inkind contributions) • Objectives, deliverables and timelines determined by the company(ies) proposing the project • Inkind contribution determined by the company(ies) • Once approved by IMI’s Governing Board the Programme Office will launch a call for proposals to identify public partners for the project • The call process and review of submitted proposals will be independent of the company(ies)
The Role Of The Programme Office
A neutral broker: To
implement
programmes and activities in the common interest of all stakeholders To
monitor
the use of public funds and industry investment To
guarantee
fair and reasonable conditions for optimal knowledge exploitation and dissemination To
facilitate
the interaction between stakeholders, including Intellectual Property agreements To actively
communicate
and promote IMI and its activities
IMI2: The First Call
Two topics:
Translational approaches to disease modifying therapy of type 1 diabetes mellitus (T1DM)
Discovery and validation of novel endpoints in dry age related macular degeneration and diabetic retinopathy
Submission date: 12 November 2014
Translational approaches to disease modifying therapy of type 1 diabetes mellitus (T1DM)
Vilnius, 11 th September 2014
Translational Approaches To T1DM: Background
• A chronic disease affecting worldwide around 17 Million people and with highest incidence rate in Europe ( ~ 22 / 100.000/ year), with major regional differences.
• The incidence of childhood T1DM is reported to be rising rapidly worldwide, especially in the under 5 year old age group.
• T1DM is generally seen today as an autoimmune disease, but its cause is unknown (genetic susceptibility, diabetogenic trigger(s) and/or exposure to a driving antigen). • The disease is currently not preventable and no cure is available. The only available pharmacotherapy for T1DM patients is the lifelong injection of insulin.
Translational Approaches To T1DM: Aims and Objectives
• • • • •
Better Disease Biology and Translational Medicine (Target & Biomarker Identification)
Generation of a high quality and comprehensive European network of clinical and translational research centres (providing a prospective clinical trials database for T1DM) including at risk and early T1DM patients.
Establishment of systematic large-data repository enabling extensive cross functional data mining and integrated data analysis Phenotypical characterization (in silico based on medical records as well as active through experimental medical studies) Systematic prospective and retrospective launch of broad “–omics” characterization of human biological samples Development and characterization of the most appropriate preclinical T1DM model(s) for discovery of novel clinical therapies.
Translational Approaches To T1DM: Aims & Objectives
• • •
Innovative clinical trial paradigms for preventative and disease
• modification trials in T1DM.
Development of standardized entry criteria and endpoints for T1DM trials (both metabolic and immune profiles) with participation of patient advocacy groups, and regulatory authorities. Implementation of the use of electronic data capture devices to collect an array of “real world data” Testing and development of novel bio-statistical methodologies applicable to new compositions of relevant end points for T1DM clinical trials. Evaluation of novel mono- and combination approaches (i.e. combining multiple immune modulatory approaches, immune cell migration modification, immune tolerance inducers, β-cell enhancing therapeutics) in people with T1DM.
Translational Approaches To T1DM: Key Deliverables
• • • An improved understanding of the immunological and beta cell biology aspects of T1DM to disentangle its heterogeneity both in at risk and early diagnosed patients and for staging participants in future T1DM clinical trials.
• The development of novel and relevant endpoints & readouts for T1DM clinical trial based on clinical & standardised molecular “real world data” obtained from T1DM patients, and on the application of novel bio-statistical methodologies.
Pre-clinical T1DM models with improved translational value.
Improved understanding of the human T1DM disease biology and optimised clinical trial setting to allow testing novel mono- and combination approaches in T1DM.
Translational Approaches To T1DM:
EFPIA PARTICIPANTS AND ASSOCIATED PARTNERS
Sanofi (coordinator), Juvenile Diabetes Research Foundation (JDRF) (co-coordinator), Novo Nordisk, Eli Lilly, GSK, Helmsley Charitable Trust.
DURATION OF THE PROJECT
The indicative duration of the project is 84 month (7 years).
BUDGET
EFPIA and associated partners: EUR 17 630 000 IMI2 JU:
EUR 17 630 000
Total: EUR 35 260 000
Translational Approaches To T1DM:
• • • • • •
APPLICANT CONSORTIUM
Academic endocrine clinics and associated supporting departments Basic, translational, and clinical researchers from the fields of T1DM autoimmunity and β-cell biology Drug discovery and medical staff in Pharmaceutical Industry and Small and Medium size Enterprises Hands-on data base specialists and big data managers Patient organizations/representatives Experts in regulatory science and health technology assessment preferably representing European health authorities.
The project will be expected to establish a T1DM Patient Advisory Committee
Translational Approaches To T1DM: Suggested Work Plan
• • A plan for interactions with Regulatory Agencies/Health Technology Assessment bodies with relevant milestones and appropriate resource allocation should be included Synergies with other EU and global initiatives, including IMI projects
Discovery and validation of novel endpoints in dry age-related macular degeneration and diabetic retinopathy
Vilnius 11 th September 2014
Novel Endpoints For Retinal Diseases
• Retinal diseases among leading causes of blindness worldwide Age-related macular degeneration (AMD): Early form reported to occur in 30% of the population of 75 years and above (over 50% by age 80); late form in 4 8% of the population over 70 years Approximately 93 million affected by diabetic retinopathy (DR) in 2010 • Limited treatment options for dry form of AMD or DR • Major development hurdles: lack of suitable endpoints for early exploratory and pivotal clinical trials, lack of predictive markers and models
Novel Endpoints For Retinal Diseases: Aims & Objectives
• •
To evaluate novel endpoint candidates for dry AMD and DR:
technical, medical and health economic appropriateness bridging preclinical and clinical studies. • • • • • •
Methods in scope:
Visual function testing beyond Best Corrected Visual Acuity (BCVA) Electrophysiology Imaging methods to assess retinal structure Soluble and genetics biomarkers Patient reported outcome tools and Quality of Life-related endpoints A combination of these methods
Novel Endpoints For Retinal Diseases: Key Deliverables
Generation of robust data resulting from retrospective and/or prospective studies as basis for discussion of regulatory acceptability of the endpoints for future clinical programmes. • • • • • It is expected that the proposed research program delivers data on: Technical evaluation of methods (validity, repeatability, reliability, interpretability, translatability and acceptability by patients) Development of novel methods and tools Clinical validation of methods/tools in patient studies for dry AMD & DR Collection of biomarkers for selection of high risk populations Synergies between dry AMD and DR vs condition-specific aspects
Novel Endpoints For Retinal Diseases:
EFPIA PHARMA PARTICIPANTS AND OTHER PARTNERS
Bayer HealthCare (coordinator), Sanofi, Novo Nordisk, Zeiss
DURATION OF THE PROJECT
The indicative duration of the project is 60 month (5 years).
BUDGET
EFPIA and associated partners: EUR 7 000 000 IMI2 JU:
EUR 7 000 000
Total: EUR 14 000 000
Novel Endpoints For Retinal Diseases:
Setting-up & running of studies required to meet topic’s objectives Multidisciplinary applicant consortium with a track record of • Clinical expertise in ophthalmology • Clinical research experience • Access to patients and databases • Public health expertise • Health economic expertise • Understanding of pre-clinical models in ophthalmology • Biomarkers • Data management • Regulatory, ethics, patients and project management
Novel Endpoints For Retinal Diseases: Suggested Work Plan
• Architecture for the full proposal to be suggested by the Applicant consortium • Intention to set-up of an Advisory panel to the Consortium comprising payers, regulatory agencies and other relevant expert advisors • Plan for interactions with Regulatory Agencies/Health Technology Assessment bodies expected • Synergies with other EU and global initiatives, including IMI projects
IMI2 Info Day
Crowne Plaza Hotel, Brussels, Tuesday 30 September 2014
• • • • • Workshops and presentations of topics by the topic writers Overview of IMI 2 funding and intellectual property (IP) rules Tips on applying for funding under IMI 2 Networking opportunities IMI staff on hand to answer questions
We warmly encourages small and medium-sized enterprises, mid-cap businesses, patient organisations, regulatory authorities, academic teams, industry, hospitals and other organisations
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