Gepersonaliseerde gezondheidszorgVan utopie tot realiteit

Personalised HealthcareHype or reality?

Rob Geraerdts

Personalised Healthcare (PHC)Is it more than a media reality – hype – or will it truly develop ?

Personalised medicine may be our future approach

Targeted drugs: The race is on

Targeted cancer drugs gain backers

Personalised drugs draw biotech dollars

Personalised approach to cancer

Personalised medicine: New approach to staying well

‘Targeted‘ drugs prove powerful against forms of cancer

FDA acts to foster ‘personalised drugs`

The Challenge of Personalised Healthcare

What the public came to expect of PHC are truly individualised therapies – something science and industry may not be able to deliver for some time

Source: JAMA. 2006;296:1453-1454.

Same symptomsSame findingsSame disease

Same Drug...

...different effects

Variability of diseaseDrug metabolismDrug-drug interactionsNon-compliance

Why a new approach to staying well is required ? What's the challenge and promise of Personalised Healthcare?

Development towards A More Personalised Healthcare

Using clinical differentiators to achieve optimal pharmaceutical efficacy and safety for the purpose of creating sustainable clinical benefits

Still today, almost all patients are treated in a few similar ways

Increasingly, treatment will be tailored to patient groups defined by their genetic disease pattern

Therapeutic stratification

Personalised HealthcareNot a totally new concept but an evolution

Today

Diagnosis and treatment expanded with rapidly growing insights into molecular processes and variations in our genes

For more than 10, 000 years

Diagnosis and treatment based on what could be seen, smelled, tasted, palpated or intuited

The last 100 years

Diagnosis and treatment expanded with knowledge about biochemistry and cellular processes

Challenges for the Healthcare system

Technological development and evolution in Diagnostics

Potential future role for the General Practioner

Costcontrol

Quality

of Life

Best medical

practice

Health Economic Value of Medical DevicesThe outside world is changing

Cost pressure

Medical innovation

Aging population Borderless world

IT revolution

Empowered people withincreased health consciousnessand demands to the system

Involvement of all players in the creation of health networks that form strong health care brands.

Payers controlling providers and redistributing costs to people Providers forced by people and payers to change the way they perform medical practice

Payers

Peo

ple

Provid

ers

Challenges for the Healthcare system

Technological development and evolution in Diagnostics

Potential future role for the General Practioner

Personalised Healthcare: hype or reality?Evolution in literature of definitions for In Vitro Diagnostics

In Vitro Diagnostics are Medical Devices which enable analysis of bodily fluids and tissues for determining disease conditions

In Vitro Diagnostics are enabling technologies to structure tomorrow's health care processes based on medical evidence

In Vitro diagnostics are a valuable tool for preventing illness, for early diagnosis and for

optimising therapy through patient monitoring and/or stratification

Personalised Healthcare: hype or reality?The need for health information as basis for medical decisions

Today:

Tomorrow:

• Tests with blood, liquid and tissue

• Health information

- „the right information in the right place at the right time“

- individual patient treatment (i.e. test result, risk profile, treatment recommendation)

- transition of today's IVD products into specific biomarkers

Result Standardisation

Novel Content

ImprovedInformation

Reagents

Systems

Laboratroy Organisation

Total IVD infrastructure( Lab Network / IT )

Re-engineeringMedical Processes with IVD

Pro

du

cti

vit

y

investments

- Reagent harmonization- Robustness improvement- Result standardisation

- System portfolio- Professional System Service

- IT solutions-Hospital solution

- DRG’s- Indication management- Personalised Health Care

- Increase laboratory productivity

Personalised Healthcare: hype or reality? How did technological development in IVD testing contribute to creating value in the laboratory ?

Therapymonitoring

toring

Therapydecision

DiagnosisPreventivemeasures

Tools

CO

NT

EN

T

Predispositionscreening

Targetedmonitoring

Personalised Healthcare: hype or reality?Populating the laboratory health value chain with tools and content to create personalised healthcare

TO

OLS

TO

OLS

InstrumentsInstrumentsand Reagentsand Reagents

DecisionAlgorithmsRisk Stratification

Algorithms Databases

Data Management Systems

DecisionAlgorithms

InstrumentsInstrumentsand Reagentsand Reagents

InstrumentsInstrumentsand Reagentsand Reagents

PortableSensor Platform

Risk profile analysis

Risk alertsDecision

Algorithms

Personalised Health Information

Current OfferingCurrent Offering

Supporting and Integrative Services

+

Personalised Healthcare: hype or reality?More fundamental knowledge of the "system biology" increases our understanding for underlying causes for diseases

DNA (gene)

mRNA (transcript

)

protein

genome transcriptome

proteome

genomics transcriptomics proteomics

Bioinformatics

Personalised Healthcare: hype or reality?To unveil the secrets of the "system biology" novel technologies are to be developed – used for diagnostic purposes

Ascher Shmulewitz et al, Nature Biotechnology – March 2006

Personalised Healthcare: hype or reality?To understand "system biology", convergence of novel technologies will provide the full potential to understanding disease patterns

Personalised Healthcare: hype or reality?"Systems biology" transparency in disease processes

Confirmatory Phase

Dx launch/ Post-launch assessment

Biomarker development

Creating PHC from an industrial perspectiveDiagnostics input is key - from discovery to market of pharmaceuticals

Target Selectio

n

Exploratory PhaseDiscove

ryPhase

Research

Companion diagnosticfeasibility & attractiveness

Tailored prescribing & monitoring

Target identification

Patient selection

Research assay Technically validated assayClinically validated IVD assay

Develop CommercialiseLead

Generation/

Optimisation

Phase 0 Phase I Phase II Phase III FilingMarket

Phase IV

PoC

Personalised healthcare: hype or reality?Understanding of disease "genetic" pattern will drive usage of new technologies in Diagnostics

Examples

* under development

Parameters (eg, Genes, Mutations)

1 10 100 1000

Genotyping Examples:

Expression Examples:

PCR Linear Arrays Microarrays

Point Mutations; Simple Gene Analysis

Complex Gene Analysis Resequencing

Single parameter “Expression”:

Complex Expression:

•CYP450 2C9

•Factor II/V

•CF Linear Array (US)

•AmpliChip CYP450Test (CE-IVD)

•AmpliChip p53*

•Taqman HIV Monitor•Taqman HCV Monitor

•Leukemia*•Breast Cancer•Cardiovascular Disease

Personalised Healthcare in the market todayCurrent examples in oncology

• Implementing biomarker strategy for all pipeline drugs

• Distribution of K-RAS and EGFR Cancer Mutation Tests– Tests identify genetic mutations that can affect patient response to certain cancer drugs

• Identifying patients who have an improved response to launched drugs

– e.g. Tarceva in 1st line maintenance NSCLC / SATURN trial

• Assessing opportunities for companion diagnostics– Pertuzumab/HER dimerization inhibitors: Expression of HER

2– MDM2: Active only in p53 wild-type patients– PLX4032: Presence of BRAF V600E gene mutation

• Detecting Hepatitis C virus subtype and monitoring viral load/ Pegasys response

– Determine length of treatment by strain of virus

– Monitor viral load to determine likelihood of response and aid in compliance

Personalised Healthcare today in the marketCurrent examples in virology

• Determining genotype 16 and 18 of Human Papilloma Virus

– Reduce risk of cervical cancer by closer monitoring

– Support Roche Pharma studies on therapeutic vaccines

Personalised Healthcare in the market todayIAT-Beispielliste

1. Invirase; 2. Crixivan

Oncology

TamoxifenTamoxifenTamoxifenTamoxifenChemotherapyArimidexHerceptinXeloda 6-MercaptopurineGleevec (CML)Gleevec (GIST)DasatinibIressaTarcevaIrinotecanErbituxRetinoic acidMabTheraTykerb

ER/PR StatusBRCA1BRCA2CYP2D6Oncotype DxER/PR statusHER2 assayEnzyme activityTPMTBCR-ABLC-KitBCR-ABLEGFR StatusEGFR/HER1UGT1A1 EGFR statusPML/RAR geneCD20EGFR status

CNSPhenytoinVenlafaxineModafinilResperidoneAtomoxetineThioridazineLevodopaTasmarAripiprazole

CYP2C9CYP2D6CYP2D6CYP2D6CYP2D6CYP2D6COMTCOMTCYP2D6

RespiratoryProlastinTheophylline

PiZZ, PiZ PiCYP2D6

Virology/Infectious Diseases

HCV GenotypingViral LoadViral LoadViral GenotypingViral GenotypingNAT Influenza A/B testHCV EVLHCV EVL

Pegasys/CopegusHIV Prot. Inh. (1st to mkt)1

HIV Prot. Inh. (2nd to mkt)2

HIV Prot. Inh. (1st to mkt)1

HIV Prot. Inh. (2nd to mkt)2

IsoniazidTamifluPegintronARoferon

CellceptAzathioprineNeoral (Cyclosporine)Prograf (Tacrolimus)Rapamune (Sirolimus)Mabthera

IATPMTIA’s for CsAIAIARA profiles

Autoimmune and Transplant

OmeprazoleProton pump inh. and Antibiotics

CYP2C19H Pylori

GIT

Cardiovascular

BiDiLHydralazineProcainamideGPIIb/IIIaStreptokinase

EthnicityNATNATTroponinTroponin

Succinylcholine Pseudochol-Inesterase levels

Anaesthesia

Metabolic and Vascular DiseaseFosamaxSomatropinInsulinSimvastatin

P1NPChr 15 HbA1cLipid profiles

WarfarinWarfarinHeparinEPO

CYP2C9VKORC1APTTCBC

Haematology

Challenges for the Healthcare system

Technological development and evolution in Diagnostics

Potential future role for the General Practioner

Personalised Healthcare: hype or realityThe proven promise of personalised health care is to further improve effectiveness of treatmentEffectiveness of treatment can be improved…

• 20-75% of patients do not receive effective treatment1

• >100.000 deaths/yr from adverse drug reactions in US2

…by tailoring treatments to selected patient groups defined by biomarkers1 Spears et al., Trends Mol Med, 2001

2 Lazarou et al., JAMA, 1998

Genom

ic

s

Prot

eom

i

cs

Patient StatusLik

elih

ood

of

treatm

en

t su

ccess

for

the in

div

idu

al p

ati

en

t

Today

Future

Cost

Effec

tiven

ess

lower

higher

asymptomatic symptomatic

higher

lower

Today diagnostics often addresses end stages of diseases. Here (e.g. late cancer phase) treatment is expensive and may not cure the patient.

New markers for the disease onset change this picture dramatically. Health care cost go down and treatment success improves.

This is were marker identification programs like proteomics and genomics come in.

New testing algorithms – A new paradigm shift in "how to treat" patientsEarlier, better diagnosis allowing for better and cost effective treatment – Early patient stratification

Risk Assessme

nt

Personalised healthcare: hype or reality Role of the treating physician across the healthcare value chain

Predisposition for

developing disease

Therapy adaptation

Patient Stratification / Therapy Selection

Screening/ Diagnosis Prognostic Predictive

Monitoring

Early detection

Predict probable disease course

Predict likely

response to a drug

Monitor efficacy/

recurrence

Healthy Asymptomatic disease

Chronic disease CuredSymptomatic disease

Personalised Healthcare: hype or reality? Benefits for patients and healthcare system

Physicians & Providers

Maximum benefit,minimum toxicity

Regulators & Policy Makers

Increased efficacy & safetyReduced healthcare costs

Payers & Reimbursers

Efficient use of healthcarebudgets

Patients

Best treatment