HARMONY – IMI Big Data for Better Outcomes for Hematologic

HARMONY, X Conf. de Plataformas Tecn. de Inv. Biomédica, Madrid 7 Marzo 2017

HARMONY – IMI Big Data for Better Outcomes for Hematologic Malignancies

Jesús M Hernández Rivas


IMI: Largest EU Public Private Partnership for Health R&D

■ 1:1 funding, joint decision making

■ All EU funds go to SMEs, academia, patient organisations

■ Pharmaceutical industry matches contribution in-kind

■ 3.400 M€ in IMI-2

■ IMI-2 not limited to pharmaceutical industry (NGS, IT, medical devices, diagnostics)

IMI2


11 Calls for Proposals under IMI-1 spend €2 billion

€ 1 945 135 308

€ 759,185,796 Infectious diseases

€ 214,136,227 Drug discovery

€ 182,980,698 Brain disorders

€ 116,880,300 Metabolic disorders

€ 116,287,312 Drug safety

IMI funding

Corporate contribution

€ 69,739,527 Inflammatory disorders

€ 55,930,958 Biologicals

€ 49,310,000 Geriatrics

€ 37,966,496 Lung diseases

€ 37,378,289 Education and training

€ 30,601,855 Sustainable chemistry

€ 20,426,255 Drug delivery

€ 18,118,249 Drug kinetics

€ 14,910,397 Relative effectiveness

Oncology? Hematology?


IMI-1: 59 Projects Covering Wide Spectrum of Topics


IMI2 Scientific Program: Initial Five Big Themes Therapeutic Areas and Cross-cutting Themes

1. Neuro-degeneration prevention and treatment of dementia and other neurodegenerative diseases

2. Prevention and treatment of immune mediated disease Advance immunological understanding to deliver new medicines and better vaccines

3. Metabolic disorders prevention and early intervention type 2 diabetes, obesity, dislipidemia, hypertension and its complications

4. Infection control Address multidrug resistance and create incentives for renewed investment (antimicrobials, antivirals) and better vaccines

5. Translational Safety identification and development of point of care safety biomarkers and new system biology platforms to better predict toxicity and safety during early development

Differentiating Enablers for all themes

Towards early and effective patient access to innovative prevention and treatment solutions (MAPPs): • Target validation based on human biology • Stratified medicine, precision medicine • Innovation in clinical trials • Data generation and interpretation (knowledge

management) • Prevention, disease interception, patient adherence

(incl. societal acceptance of vaccines) • Effect on medical practice and outcomes

(health/disease management) • Regulatory framework (including pharmacovigilance) • Patient access


Feedback and learning

Transparent outcomes data (big and deep data sources)

Analyze variation

Identify

current best practices

Optimize treatment, Change behaviour

Improved outcomes

Reduced variation

Increased efficiency

Sustainable health care

Within IMI2, big data is a key topic as it holds significant potential to improve outcomes and drive healthcare efficiency


Leading Causes of Death in US, 1975 vs 2013 (% of All Causes of Death)


Trends in SEER incidence rates and Life Lost


Trends in SEER incidence rates and Life Lost


Genetic Signatures in Cancer

4.938.362 mutations in 7.042 patients with cancer https://cancergenome.nih.gov/

Alexandrov et al. Nature, 2013


Next Generation Sequencing studies allow a new reclassification of Cancer

Hoadley et al. Cell, 2014


HM as examples of targeted therapy

B-NHL

APL

CML

MM

B-ALL

CLL

TKI Imatinib, Nilotinib, Dasatinib

TT

Mo Ab

Proteasome inh / IMIds

BTKInh

MoAb

ATRA, ATO

Rituximab

Bortezomib, Lenalidomide

Ibrutinib

Blinatumomab

>90%

90%

>70%

>5 y

TBA

TBA

Survival


HARMONY is currently the largest program under the IMI "Big Data for Better Outcomes" umbrella

Goal: Support the evolution towards outcomes-focused and sustainable healthcare systems, exploiting the opportunities offered by large data sets from variable sources

"Big data for better outcomes"

Design sets of standard outcomes

and demonstrate value

Increase access to high quality outcomes data

Use data to improve value of HC delivery

Increase patient engagement through digital solutions

COORADINATION AND SUPPORT ACTION (CSA) (Consortium formed)

PROSTATE CANCER (Call published)

CARDIOVASCULAR (Consortium formed)

Future topic proposals, e.g. respiratory, oncology and ophthalmology

HEALTH OUTCOMES IN MULTIMORBID PATIENTS

EUROPEAN DISTRIBUTED DATA NETWORK

ROADMAP: ALZHEIMER'S DISEASE (launched)

1 2 3 4

PLANNED PROJECTS

HARMONY: HEMATOLOGIC MALIGNANCIES


Our journey so far Significant milestones … but not always easy

Topic Text Development April – July 2015

Topic Text Call Launch September 2015

HM Webinar Launch October 2015

HARMONY Proposal January 2016

Independent Evaluation, Phase I February 2016

EFPIA

HARMONY

Leadership Kick Off meeting March 2016

Madrid F2F HARMONY April 2016

Submission Deadline June 14 2016

MAY JUN JUL AUG SEP OCT NOV DEC JAN FEB MAR APR MAY JUN 2015 2016

JUL AUG SEP OCT NOV DEC JAN 2017

Independent Evaluation, Phase II July 2016

Negotiation Phase July-November 2016

CA & DoA December 2016

Kick Off Jan 2017

FEB MAR APR

Original Idea Feb 2015



HARMONY: public-private partnership 51 partners, including 44 public partners, from 11 different European countries

Healthcare Alliance for Resourceful Medicines Offensive against Neoplasms in HematologY

Pharma Regulators / HTAs

Medical associations

Universities

Research inst. and hospitals

Patient associations

Tech and biotech

http://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjrrIr2h63QAhVCOBoKHVK5Cq8QjRwIBw&url=http://www.altoroslabs.com/customers_speak.html&psig=AFQjCNGFotaQsVCKmhrF4NEtjEoLN06zLg&ust=1479378339681869

https://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwintoGKhK3QAhXQhRoKHY02DK0QjRwIBw&url=https://www.eureporter.co/health/2016/10/20/eapm-bucharest-hosts-key-conference-on-personalised-medicine/&psig=AFQjCNF42obUgt41H9JJWx78tKh7YnSWnQ&ust=1479377308115244

http://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiK2P-cia3QAhWDOBoKHSIeCLcQjRwIBw&url=http://www.kinderkrebsinfo.de/aktuelles/termine/index_ger.html?record_id=e147529&bvm=bv.138493631,d.d2s&psig=AFQjCNFS8156AZmRg9BY-MLBn8jLOS0f6A&ust=1479378679579416

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https://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwi-2YPrh63QAhWFnRoKHYJ0C3MQjRwIBw&url=https://impact.cjv.muni.cz/pracoviste/&psig=AFQjCNGZhy66FikKlmFvHXOoQFSyowsiEQ&ust=1479378304959460

http://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiHkuqZiK3QAhVHNhoKHaveArYQjRwIBw&url=http://www.meta-net.eu/participating-organisations/5d1e0d66e737aef9ad88f1e14e063f13&psig=AFQjCNFstS12AUBp3f7O5upcGP5MogZdpg&ust=1479378401976212

https://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjypMuxiq3QAhWGrxoKHbmtBnsQjRwIBw&url=https://www.magbuzz.de/3/goethe-uni-frankfurt.html&bvm=bv.138493631,d.d2s&psig=AFQjCNGqW46IQdtchdT0aNbJaRs1Z3vAdw&ust=1479378981329543

http://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjOvI69iq3QAhUFHxoKHS7-CUIQjRwIBw&url=http://91.206.61.24/en/ludwig-maximillians-universitaet-muenchen.php&psig=AFQjCNEA8M95GbCkcyWSXbrBVlLxeZyUeg&ust=1479379023290255

http://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwixi5rIiq3QAhXGORoKHT96DNoQjRwIBw&url=http://health-gradient.eu/home/partners/institut-fur-medizinische-soziologie/&psig=AFQjCNEW8zXcxCbPayH0UlgFhZg9IOrxnA&ust=1479379048840637

http://www.wikiwand.com/en/European_Organisation_for_Research_and_Treatment_of_Cancer

http://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiCwJHBhK3QAhUBWxoKHZc1B7AQjRwIBw&url=http://www.immunology.be/congress/signaltransduction/index.html&psig=AFQjCNG78sI5RXVrrSeMi5Z1yA0hJX2tug&ust=1479377420156448

http://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjRxpOqiK3QAhWPyRoKHQ8oDngQjRwIBw&url=http://www.excilone.com/86--.html&psig=AFQjCNHKkU5W4DJ1R_wkGizP0CTTdmbMOA&ust=1479378448786429

http://www.graall-leukemia.fr/index.php

http://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwj--9rViK3QAhWCSxoKHTKjArgQjRwIBw&url=http://www.lysa-lymphoma.org/en/contact-2/&bvm=bv.138493631,d.d2s&psig=AFQjCNEsX5XUSVhG6YD2_Uu_X_suQRXIUA&ust=1479378541210377

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HARMONY Executive Committee

Guillermo Sanz Project Co-Chair

Jesús M. Hernández Project Coordinator

Patricia van Dijck Project Leader

Pam Bacon Project Co-Leader


HARMONY aims to meet major unmet needs in HMs


Need for harmonization of outcome measures and endpoint definitions for HMs at European level

Increasing omics data available, but limited application in clinical practice

Need for speeding up drug development, access pathways and "bench-to-bedside" process


Specific outputs for Pharmaceutical companies

• facilitate drug development pipelines, accelerate the “bench-to-bedside” process in drug development by identifying appropriate targets/disease cohorts

• provide the evidence base for large co-operative studies to identify the most appropriate patient cohorts for future trial designs

• create a holistic and timely approach for innovative clinical practice by involving all stakeholders across the spectrum, from basic researchers to policy makers, in each stage of the project

• facilitate reimbursement decisions, by providing solid data and tools obtained across EU member states

• enable broader and improved collaboration between the diagnostic test developers, who are focusing on efforts for targeting early drug development, and the pharmaceutical companies


HARMONY: 8 Work Packages across 7 diseases Expert A

dvisory Panel

WP3: Data access (GMV, JANSSEN, BAYER) WP4: Data platform (ELN, JANSSEN)

WP1: Project management (IECSCYL, NOVARTIS, CELGENE, HULAFE)

WP

2: Outcom

es definition (U

ULM

, BAYER, TAK

EDA

)

WP5: Data analytics for therapies valuation (UNIBO, MENARINI, JANSSEN)

WP7: Dissemination, communication and training (EHA, NOVARTIS, TAKEDA)

WP8: Legal, ethics and governance (MUW, AMGEN, BAYER)

MM Sonneveld San Miguel Boccadoro

ALL Gökbuget Dombret

Ribera

CLL Ghia

Pospisilova Bosch

NHL Salles

Dreyling Montoto

MDS Fenaux

Kuendgen Santini

Child HM Moorman Reinhardt Locatelli

WP

6: HTA

, EMA

, patients integration

(LeukaNET, CELG

ENE, JA

NSSEN

)

Ethics Advisory B

oard AML

Ossenkoppele Huntly

Lo Coco

EFPIA experts in HM

Co-operative Working Groups (CWG)

EU hospitals & Academic partners


HARMONY: 8 Work Packages across 7 diseases

Expert Advisory Panel

Specific questions by disease Involvement of KOL + Working Groups OMICs + Clinical Data

WP1: Project management (IECSCYL, NOVARTIS, CELGENE, HULAFE)

WP

2: Outcom

es definition (U

ULM

, BAYER, TAK

EDA

)

WP5: Data analytics for therapies valuation (UNIBO, MENARINI, JANSSEN)

WP

6: HTA

, EMA

, patients integration

(LeukaNET, CELG

ENE, JA

NSSEN

)

MM Sonneveld San Miguel Boccadoro

ALL Gökbuget Dombret

Ribera

CLL Ghia

Pospisilova Bosch

NHL Salles

Dreyling Montoto

MDS Fenaux

Kuendgen Santini

Child HM Moorman Reinhardt Locatelli

AML Ossenkoppele

Huntly Lo Coco

WP3: Data access (GMV, JANSSEN, BAYER) WP4: Data platform (ELN, JANSSEN)


What makes HARMONY different from other projects?

Big Data

Clinical data 7000 7500 4000 5600 5500 6000 8000

Immunofluorescence 4000 1500 3750 2000 3000 5000

Cytogenetics 5000 4500 3750 4000 1000 4000 4000

“Omics” 2800 2800 1200 1700 1600 1500 3000

MM AML ALL CLL NHL MDS Child HM

EFPIA Companies

KOLs

Working Cooperative Groups (WCG)

Associated Members and Other sources

Dat

a Q

ualit

y Su

perv

isio

n (W

P le

ader

s WP

1, 2

, 3, 5

) Data Custodians

1



Big Data 1 Dedicated WP6 to HTA, EMA, patients alignment & optimisation

• Constitution of a Policy Health Stakeholder Feedback Forum (PHSFF)

• Development of a Clinical Value Framework

• Development of set of outcomes relevant for decision-makers

• Health literacy: communication strategy for transfer and adoption of project results

• Patients perspective incorporated – link with EUPATI

Stakeholders involved (patients, regulators, HTA, policy makers)

2



Big Data 1

Stakeholders involved (patients, regulators, HTA, policy makers)

2

20 countries, 65+ members, 6.4 M€ budget

1

3

1 1

1

1

8

2

1

3

16

1

1

2

15

2

1 4

1

Associated members & variable budget

3


AML Proof-of-Principle Study Objectives:

1. Identification of additional gene-gene interactions and impact on outcome

& validation and further refinement of novel genomic classification

2. Evaluate the impact of “intensive therapy” on “overlap cases”, i.e. aggressive MDS cases (RAEB II) that are treated like AML

3. Evaluate genomic information with regard on chemotherapy side effects, infectious complications, etc. 4. Determine impact on allogeneic transplantation


Prototype:

⇒ Individual risk prediction depending on different treatment options

Gerstung/Papaemmanuil et al. Nat Genet 2017

AML ”Knowledge Database“ WP2 - WP5 interaction


Prognostic factors of treatment with hypomethylating agents (HMAs) in high-risk MDS Azacytidine or decitabine Chemo or SCT Mutational analysis Several WCG

MDS

Projects in HARMONY

Create novel prognostic/predictive scheme for improved risk stratification aimed at personalized medicine

Mutational analysis ERIC

CLL

What is the most efficient way to integrate risk factors to improve patient risk stratification? Several WCG including iBFM/AIEOP

Pedi atrics

“Curable” Myeloma MM T-Cell NHL Clinical characteristics Mutational analysis

NHL


The patient is at the center of HARMONY: Collaboration of all stakeholders needed to meet patients' needs

Hematologists BioinformaticiansData scientists &

ICT

Economists Patients Policy makers

Regulators HTAs

Pharma Industry

Ethics


1. First IMI Project in Hematological Malignancies.

2. A comprehensive Project focused in Hematological Malignancies.

3. To integrate Big Data Series of patients with high-quality data.

4. Stakeholders involvement: Payers, HTAs, Regulators and Patients.

5. Open project: Pharmaceutical companies, Working Cooperative Groups and

Hospitals are welcome.

HARMONY Summary



EHA, Madrid, 23 June 2017

HARMONY, Berlin, 23 October 2017

ASH, Atlanta, 10 December 2017

HARMONY: Future Awareness Meetings

1

2

3

HARMONY, X Conf. de Plataformas Tecn. de Inv. Biomédica, Madrid 7 Marzo 2017 HARMONY, Kick-Off Meeting, Salamanca, Jan, 2017

Documents

HARMONY – IMI Big Data for Better Outcomes for Hematologic