Future of Personalised Medicine and its role in making healthcare sustainable

Exeter College symposium Professor Richard Barker

Director, CASMI 1

Key points

Why healthcare is unsustainable Medical innovation: problem or solution? New biomedical science and the innovation

gap The four ‘gaps in translation’ and how to

bridge them Personalised medicine as a major contributor

to sustainable healthcare

2

Key points

Why healthcare is unsustainable Medical innovation: problem or solution? New biomedical science and the innovation

gap The four ‘gaps in translation’ and how to

bridge them Personalised medicine as a major contributor

to sustainable healthcare

3

5.0

7.0

9.0

11.0

13.0

15.0

17.0

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

USA

Belgium

Denmark

France

Germany

Greece

Ireland

Italy

Netherlands

Norway

Portugal

Spain

Sweden

Switzerland

UK

Japan

>2% increase

1.5% increase

Health expenditure as a percentage of GDP

Source: OECD

2010 2010 2030 2030

Healthcare costs

Supply forces Demand forces

Aging populations

Higher expectations

Lifestyle-driven disease

New infectious diseases

Several powerful demand drivers

Not this …. But this …. And even this ….

Great expectations …

Self-inflicted disease … obesity …

Deaths, Men 45-64

Other Europe Scotland

England & Wales

Alcoholism ….

Unpredictable pandemics add predictable costs

Historical growth rate

Aging population

Greater expect-ations

Negative lifestyle changes

New technologies

2.5 – 5.0%

1%

1-2%

1%

1-2% 6 – 9%

Demand and supply drivers combine to create unsustainable real terms growth

Socialised systems: unacceptable tax burden

Private insurance: Unaffordable premiums

Both: reduced coverage and/or greater co-payments

Key points

Why healthcare is unsustainable Medical innovation: problem or solution? New biomedical science and the innovation

gap The four ‘gaps in translation’ and how to

bridge them Personalised medicine as a major contributor

to sustainable healthcare

12

2010 2010 2030 2030

Healthcare costs

Supply forces Demand forces

Biotherapeutics

Gene and cell therapies

Molecular diagnostics

Imaging

Implantable devices

Major information projects

Supply of new technologies also adds to healthcare costs

Key points

Why healthcare is unsustainable Medical innovation: problem or solution? New biomedical science and the innovation

gap The four ‘gaps in translation’ and how to

bridge them Personalised medicine as a major contributor

to sustainable healthcare

14

Disruptive technologies and ideas

Tools & technologies Next generation sequencing Biomarkers for stratified

medicine In vitro toxicology Pathway and organ e-

simulation Electronic clinical trial

monitoring EMRs and real world data

analysis (‘Big Data’) Mobile health apps

Ideas Open innovation Crowd-sourcing solutions Patient group initiatives &

leadership Bayesian analysis Adaptive licensing Flexible regulatory routes Patient need/concern

profiling Patient-reported outcomes

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Research

Clinical Development

Real World Application

Genetic links to disease -

Genetic links to disease -

Diseases and Traits with Published GWA Studies • Macular Degeneration • Exfoliation Glaucoma • Lung Cancer • Prostate Cancer • Breast Cancer • Colorectal Cancer • Bladder Cancer • Neuroblastoma • Melanoma • TP53 Cancer Predispos’n • Chr. Lymph. Leukemia • Inflamm. Bowel Disease • Celiac Disease • Gallstones • Irritable Bowel Syndrome • QT Prolongation • Coronary Disease • Coronary Spasm • Atrial Fibrillation/Flutter • Stroke • Subarachnoid Hemorrhage • Intracranial Aneurysm • Hypertension • Hypt. Diuretic Response • Peripheral Artery Disease

• Syst. Lupus Erythematosus • Sarcoidosis • Pulmonary Fibrosis • Psoriasis • HIV Viral Setpoint • Childhood Asthma • Type 1 Diabetes • Type 2 Diabetes • Diabetic Nephropathy • End-St. Renal Disease • Obesity, BMI, Waist, IR • Height • Osteoporosis • Osteoarthritis • Male Pattern Baldness • F-Cell Distribution • Fetal Hgb Levels • C-Reactive Protein • ICAM-1 • Total IgE Levels • Uric Acid Levels, Gout • Protein Levels • Vitamin B12 Levels • Recombination Rate • Pigmentation

• Lipids and Lipoproteins • Warfarin Dosing • Ximelegatran Adv. Resp. • Parkinson Disease • Amyotrophic Lat. Sclerosis • Multiple Sclerosis • MS Interferon-β Response • Prog. Supranuclear Palsy • Alzheimer’s Disease in ε4+ • Cognitive Ability • Memory • Hearing • Restless Legs Syndrome • Nicotine Dependence • Methamphetamine Depend. • Neuroticism • Schizophrenia • Sz. Iloperidone Response • Bipolar Disorder • Family Chaos • Narcolepsy • Attention Deficit Hyperactivity • Personality Traits • Rheumatoid Arthritis • RA Anti-TNF Response

Diabetes

HLA Type I Monogenic diabetes (rare variants)

MODY

GCK

HNF1A HNF4A HNF1B IPF1 NeuroD1

INS CEL MODY X

Type II (Common variants)

Neonatal

6q ZAC KCNJ11 ABCC8 INS GCK

HLA

Predicting personal risk …

Disease

Personal disease prevention

Seven markers in blood

And full sequencing is dramatically falling in cost and time…

Source: Forbes

Epigenetics imprints our health history on our genes …. And our childrens’ genes

2025 drug targets

Gene – disease associations Protein structures determined

Advanced genomics and proteomics are yielding many drug targets

The Innovation Gap

time

progress Bioscience – understanding human biology and disease = potential patient benefit

Actual patient benefit

The Innovation Gap

Pharmaceutical R&D Productivity

The danger of doing nothing

progress Bioscience – understanding human biology and disease = potential patient benefit

Actual patient benefit

time

- First ever industry reduction in R&D spend - $4bn drop in overall US spending in 2011

Key points

Why healthcare is unsustainable Medical innovation: problem or solution? New biomedical science and the innovation

gap The four ‘gaps in translation’ and how to

bridge them Personalised medicine as a major contributor

to sustainable healthcare

28

• Basic bioscience

Translation to clinical candidates

• Innovations in clinical trial

Regulatory & reimbursement

approval • Approved products

Uptake by health systems

• Innovations used by patients

Patient Benefit

Addressing the the four “gaps in translation”

Translating research into candidate products: New ‘open innovation’ models; IP law; governance; business economics; public policy

Improving productivity of clinical development: Adaptive licensing approaches: statistics; ethics; trial design; regulatory science; health economics

Ensuring effective diffusion and adherence: Behavioural health; psychology; sociology

Feeding back from clinical outcomes to R&D: Big Data analysis, statistics, epidem-iology

Gap 2

Gap 1 Gap 3

Gap 4

Current development path

I II IIIa Review HTA

IIIb IV

PoC Ph III entry Launch

Key characteristics of current model • Inflexible processes and methods • Expensive, increasing data demands • Lack of early alignment between key parties: • Segmented input & decision making • Access Needs- not designed in • Patient perspective - not fully addressed

FIM P&R

Access

PV & RM

External activities

Sponsor activities

Submission NDA

Potential new flexible blueprint

Exploratory R & D Review & design Confirmatory trials

Effectiveness/comparative studies

Submit & Confirm approval

Initial Access

Key Features:

-Basic division between exploratory and confirmatory trials rather than Phases I-IV

-Collaborative design step before the most expensive confirmatory trials are commissioned

-Ability/need to customise the model for different benefit/risk/uncertainty profiles

-Early, controlled patient access if justified by interim findings of confirmatory trials

-Subject to requirements for pharmacovigilance and pharmacoeconomic analysis before full ‘green light’ for wide access and longer term reimbursement policy

Key points

Why healthcare is unsustainable Medical innovation: problem or solution? New biomedical science and the innovation

gap The four ‘gaps in translation’ and how to

bridge them Personalised medicine as a major contributor

to sustainable healthcare

32

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Personalised treatment for cystic fibrosis

Disease segmentation has great benefit

Lilly Jaffe

Cameron Lundfelt

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= Centre for the Advancement of Sustainable Medical Innovation

=

www.casmi.org.uk