Post on 28-Jul-2020
Innovative Medicines Initiative
The European Union and the pharmaceutical industry
have joined forces to make
drug R&D processes in Europe more innovative and efficient,
enhance Europe’s competitiveness
& address key societal challenges
by forming
the biggest PPP in Life Science
2
Innovative Medicines Initiative: Joining forces in the healthcare sector
Pooling expertise, knowledge and resources
Developing incentives to address major
unmet medical needs
Providing a neutral trusted platform to align
public and private interests
Public-Private Partnerships: Why ?
IMI accelerates the development of new therapies for major yet unmet public health needs and
diseases where treatments are lacking
The Anti-Microbial Resistance Conundrum
- Anti-microbial resistance kills 25 000 European citizens every year
- Annual costs are estimated at €1.5 billion
- Only 2 new antibiotic classes developed over the last 30 years
- Low level of industry investments in antibiotic innovation
How IMI addresses infectious diseases
Invested €229 million in projects aiming at:
Solving scientific challenges
Fostering new models of industrial collaborations for antibiotics and diagnostics development
Developing networks for clinical trials
Revisiting regulatory environment
Providing necessary incentives for industry to reinvest in the area
COMBACTE CLIN-Network 280 members and Candidate members
Improved detection of infectious diseases
RAPP-ID is developing Point-of-Care Tests (POCTs) for rapid (hospital <2h,
primary care <30min) detection of bacteria, mycobacteria, fungi and viruses
Developed conceptual POCTs platforms for community-acquired pneumonia, influenza, tuberculosis
Designed conceptual POCs for the detection of antibiotic resistance for Ventilator-Associated Pneumonia and tuberculosis
Developed a diagnostic device and protocol related to breath-born aerosol sampling - patent application filed
Concept RCA module chip
5 EFPIA companies; 10 Public organizations; 4 SME Total Budget: 14.4 Mi €
The conundrum of brain disorders
Brain disorders affect 1 in 3 Europeans And cost the economy € 798 billion / year
Developing new drugs to treat brain disorders takes longer, costs more than
for other diseases
There are few effective treatments in this area
IMI projects are tackling these issues
How IMI addresses brain disorders
Invested €148 million in projects aiming at:
Shedding new light on the underlying causes of autism (EU-AIMS)
Combining data to pave the way for new treatments for schizophrenia & depression (NEWMEDS)
Identifying new targets for drugs for chronic pain (Europain)
Developing models to predict the efficacy of drug candidates in Alzheimer’s patients (PHARMACOG)
Revisiting regulatory environment for drug development
Providing necessary incentives for industry to reinvest in brain disorders
Identified brain functional abnormalities that can be reversed in ASD patients by modulating brain 5HT - outcome predictor for clinical trials
Identified significant differences in cortico-cortical anatomical connectivity in ASD patients - outcome predictor for clinical trials
Identified significant differences in brain functional response to emotional sounds in infants at risk for autism - risk predictor
Published first study of EU wide prescribing in ASD
Advances in Autism
6 EFPIA companies; 15 Public organizations; 3 SME 1 patient org; Total Budget: 35.9 Mi €
2 Largest Clinical Trials for Early Detection and Monitoring of ASD Children
Identification of biomarkers that precede ASD onset
− Prospective study of 300 high-risk infants (3 and 7 months) with older siblings with ASD, and 100 low-risk
− Infant cognition, behavior, neuroimaging, neurophysiology
− Relation to symptoms/diagnosis of ASD at outcome
Accelerated longitudinal study for validation of ASD biomarkers in children and adults
− 450 ASD patients and 300 controls
− magnetic resonance imaging, event-related potential, eye-tracking
Preclinical Alzheimer’s disease
Findings in preclinical Alzheimer’s disease:
common in cognitively normal elderly people
can be diagnosed by cerebrospinal fluid markers
associated with future cognitive decline and mortality – therapeutic target
9 EFPIA companies; 36 Public organizations; 7 SME 3 patient org.; Total Budget*: 53.4 Mi €
* Total budget for the EMIF program that included EMIF AD, EMIF metabolomics and EMIF platform
Platelets: APP metabolites, 55 kD and 25 kD fragments - AlzProtect
Lymphocytes: ~ 150 RNA transcripts related to Abeta pathway, inflammatory pathway and to immune mechanism - Exonhit (now Diaxonhit)
Red blood cells: binding of Abeta1-42 on cellular membrane and change in PKC conformation in red blood cells - Innovative Health Diagnostics (IHD)
Red blood cells: panel of inflammatory markers- Innovative Concept in Drug Development (ICDD)
COMPLETED RECRUITMENT OF 150 MILD COGNITIVE IMPAIRED PATIENTS FOR BIOMARKER MATRIX CLINICAL TRIAL
Novel Disease Markers for Alzheimer’s Disease
12 EFPIA companies; 13 Public organizations; 5 SME Total Budget: 27.7 Mi €
Advances in schizophrenia and depression research
Gained novel insights into the biology of schizophrenia
Standardised the cognitive models across several industrial partners
Developed novel tools for drug discovery - animal models, human imaging
Developed new web tools - image analysis, biomarker significance
Provided information for the design of more efficient clinical trials
10 EFPIA companies; 7 Public organizations; 3 SME Total Budget: 23.2 Mi €
Achievements in chronic pain
Initiated international consensus meetings on conducting preclinical trials
Conducting clinical trials to improve patient stratification
Developing tools to predict which patients will respond to treatments
Studying the placebo effect to reduce clinical trial failures
Initiated EMA interactions to frame regulatory landscape
8 EFPIA companies; 12 Public organizations; 1 SME Total Budget: 18.2 Mi €
DIABETES: Fighting the epidemic
through Public-Private Partnership
Major Public Health Need
Diabetes will affect 43 million Europeans in 2030 €89 million spent on 2011 on treating diabetes and its complications
Distrust in past-research
Cardiovascular complications of rosiglitazone and benfluorex
Hurdles to drug development
Patients’ heterogeneity Lack of reliable markers for disease activity and complications
How IMI facilitates the development of new diabetes therapies
Invested €125 million in 3 projects aiming at:
Solving scientific challenges
Developing reliable measures of diabetes activity and complications
Developing treatments tailored to the different needs of individual patients
Biomarkers of Diabetic Complications
Generated the largest ever made database of GWAS samples in diabetic nephropathy (DN) from patients with T1D & T2D - discovery of potential biomarkers
Identified multiple biomarker candidates for diabetic related kidney damage, retina damage and coronary vascular disease
Developed an ultrasound/radiofrequency-based virtual histology for non-invasive assessment of plaque structure
3 patents in preparation
6 EFPIA companies; 18 Public organizations; 1 SME Total Budget: 32.6 Mi €
Discovered a lipid signature in the serum of mice fed with high fat diet that correlates with physiological readouts – potential biomarker for diabetes
Generated the 1st human ß-cell line (EndoCBeta H1) and its beta cell phenotype maintenance has been confirmed by 3 pharma partners
Working on the 2nd generation human ß-cell lines with excisable immortality genes - more suitable for drug discovery purposes
Generated the world largest bio repository of human islets for diabetes research, with a bioinformatical analysis of the genome, transcriptome, lipidome and morphological and physiological characteristics - 138 islets
Advances in Diabetes
8 EFPIA companies; 12 Public organizations; 1 SME Total Budget: 25.9 Mi €
IMI DIABETES PLATFORM Memorandum of Understanding between IMIDIA, SUMMIT and DIRECT
for exchange of data and confidential information
IMI develops better tools to ensure the safety of existing and future medicines
Safer and Faster Evidence Based Translation
Evaluated 153 potential biomarker candidates for drug-induced
injury of the kidney, liver and vascular system
17 exploratory clinical studies started or completed
> 6500 retrospective samples collected
64 biomarker assays developed
Dialogue with Regulatory Agencies established
11 EFPIA companies; 5 Public organizations; 4 SME Total Budget: 35.9 Mi €
Development of reliable toxicity predictive systems
5th release of the Vitic Nexus eTOX database
537 substances (165 confidential) linked to 1,703 study designs
(Bayer, Boehringer, Esteve, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, Roche, Sanofi, Servier and UCB)
3rd release of the ChOX database
411 toxicology-linked targets; 162,287 distinct compounds and 701,181 activities
Version 1 of the integration system, eTOXsys, was released to all partners
7 out of 10 companies have already a running system.
90 predictive models developed
13 EFPIA companies; 8 Public organizations; 4 SME Total Budget: 13.9 Mi €
Aims to strengthen the monitoring of benefit-risk of medicines in Europe by developing innovative methods
Works to enhance early detection and assessment of adverse drug reactions from different data sources (clinical trials, spontaneous reporting and observational studies)
Is developing methods to enable the integration and visual presentation of data on benefits and risks
Delivered PROTECT ADR database of adverse drug reactions (ADRs) – 45298 ADRs for 654 medicines
Delivered the inventory of Drug Consumption Databases in Europe – 17 countries
New Methodologies in Pharmacovigilance & Pharmacoepidemiology
12 EFPIA companies; 16 Public organizations; 2 SME Total Budget: 29.8 Mi €
IMI provides a unique neutral platform for a continuous dialogue with patients, regulators,
academia and industry
Since 2009, 40 projects launched - total budget €1.2 billion
*: Estimate
*
Creation of unprecedented collective intelligence networks Collaborative publications among IMI researchers -Call 1-3
Data & analysis: Thomson Reuters (Custom Analytics & IP Solutions)
Delivering high quality research
0,0 1,0 2,0 3,0
Pharmacology & Pharmacy
Neurosciences
Mathematical & Computational …
Endocrinology & Metabolism
Biology
Research & Experimental Medicine
Clinical Neurology
Psychiatry
Overall
IMI Projects average EU average
Data & analysis: Thomson Reuters (Custom Analytics & IP Solutions)
Citation Impact by research area
Securing regulatory relevance of projects outputs via regulators’ involvement
Regulators represented in IMI projects as: Coordinator: EMA (1);
Participants: EMA (1) and other EU national Agencies (5); Advisory Board: EMA (>10) and FDA (5)
Informal interactions already established for a number of projects
EMA Qualification Advice procedures ongoing for 2 projects
IMI referred to the EMA Road Map to 2015 and more specifically highlighted in workprograms of some EMA Working Parties
Safety, Pharmacogenomics, Patients’ and Consumers’ Organisations
IMI/EFPIA held an information session for projects with EMA/FDA on the processes for Drug Development Tools advice and qualification (May 2013)
IMI actively involves patients
Aim: development of Patient Reported Outcomes that measure aspects of physical activity relevant to patients and are sensitive to changes due to treatment.
Development of tools to measure physical activity status in COPD
literature
patients
2 questionnaires
6 activity meters 2 meters
initial validation (6 wks)
reduction integration
230 patients
final validation: clinical & behavioural studies
2009-2011 2011-2012 2013-2014
re-assessment 6+12 months for seasonal effects
8 EFPIA companies; 7 Public organizations; 1 SME 3 patient org; Total Budget: 16.7 Mi €
Biomarkers for Predicting Severe Asthma Outcome
Established diagnostic criteria on severe asthma
Developed various “omics” platforms based on genetic, proteomic, metabolomic, breathomic biomarkers
Generated a preliminary phenotype ‘handprint’ by combining molecular, histological, clinical and patient-reported data
Patient cohort - 14 centres across Europe targeting 1025 subjects, to validate the handprints for their predictive efficacy in gold standard and experimental therapeutic intervention
An integrative system biology approach to understanding pulmonary diseases; Auffray et al., 2010
Diagnosis and definition of severe asthma: an international consensus; Bel et al., 2011
9 EFPIA companies; 21 Public organizations; 3 SME 5 patient org; Total Budget: 20.1 Mi €
IMI contributes to the competitiveness of the European pharmaceutical sector
1. Establishment of robust validated models for drug development
2. Identification of new drug targets
3. Tools for predictive toxicology
4. Advances in precision medicine
5. Novel, clinically relevant biomarkers
6. New patient reported outcomes (with regulatory guidance)
7. New tools for ‘big data’ management, effective data interpretation, and clinical decision support
8. Streamlining of clinical trial design and regulatory frameworks
9. Access and creation of clinical investigator networks
10. Resources for a successful translation - genes to animal models to patients
11. Investment in reclassification of complex diseases
IMI improves pharmaceutical R&D productivity
Novel in vitro methods for cancer drug discovery
Developed cancer organoid cultures - 3D cultures that preserve cancer heterogeneity
Completed cancer drug screening 10 drugs on 5 patient derived cell lines each
Developed patient derived xenograft cancer models
Discovered potential biomarkers able to predict tumor sensitivity to Afatinib (105 BM)and to Regorafenib (69 BM) treatment
7 EFPIA companies; 7 Public organizations; 4 SME Total Budget: 30.7 Mi €
Targeting Rheumatoid Arthritis
Identification and characteristics of cohorts and biobanks for different stages of RA (33 cohorts, more than 10.000 biosamples)
Identification of biomarkers for response to therapy
Standardization of existing and development of new animal models
Production of monoclonal human antibodies to autoantigenic targets in RA
Identification of new targets for therapy, including six potential miR targets that are translatable between mice and RA
Stittrich AB et al. Ann Rheum Disdoi: 2011 70: A43
10.1136/ard.2010.148981.3, presented at the EWRR
2011
9 EFPIA companies; 24 Public organizations; 1 SME Total Budget: 38.1 Mi €
Modeling and Simulation Clinical Trial Simulator - Prototype v.2
Flexible study designs for PII clinical drug development:
− parallel group studies − crossover studies − complex treatments
Simulation of patients sampled
Simulating the exposure to the investigational drug
Simulating types of drug effects related to drug exposure:
− Continuous effects − Time-to-event effects − Categorical effects − Count data as effects
Methods of evaluating the simulated trials
− Optimal sampling times − Individual probabilities or risks − Trial success
Automatic reporting
10 EFPIA companies; 10 Public organizations; 5 SME Total Budget: 21.2 Mi €
Efforts to Automate clinical
research
Regulators
Clinical Trial Management
System (CTMS)
Trial Registry
Document Management System
Clinical Data Management
System (CDMS)
1 DESIGN
Feasibility Study
2 EXECUTION
Patient Recruitment
3 EXECUTION
Data Collection
XML XML
FDA-EMEA SUBMISSIO
N
XML
XML
Protocol (CDISC PRM – SDM)
Case Report Form (CDISC ODM)
10 EFPIA companies; 21 Public organizations; 2 SME Total Budget: 16 Mi €
€38.5 million invested in Education and Training programs
More than 1000 scientists have been trained so far
Many more scientists take advantage of industrial internships
Enhanced learning experience
IMI trains a new generation of industrial scientists and regulators, and reduces the cost of continuous
professional development for companies
Catalogued >5000 masters, PhD, CPD and short courses taught in 21 languages, from 39 countries, covering over 60 scientific, therapeutic and biomedical areas from about 1000 universities.
More than 320 students participated in various courses (50% from EFPIA companies) in 2012. Provided 20 new courses in drug safety sciences.
58 students are following the flexible and fully e-learning programme covering medicines risk identification and quantification, medicines and public health, medicine risk communication, assessing the benefits of medicines, and regulatory processes.
24 universities network + 16 universities affiliates. 685 students have been following various courses (28% from EFPIA companies).
Europe’s first Patients’ Academy on Therapeutic Innovation aiming to provide scientifically reliable information on medicines and R&D, as well as an online public library that will empower patients to engage more effectively in the development and approval of new treatments and become true partners in pharmaceutical R&D.
IMI Education and Training programs > 1000 trainees so far
Draft available at http://bit.ly/1axI076
Comments and suggestions are welcome: SRAconsultation@efpia.eu
Strategic Research Agenda for IMI2:
The right prevention and treatment for the right patient at the right time