Personalisierte Medizin in der Praxis - DVFA · Erbitux ® (cetuximab) Breast ... Identified 60% pts (KRAS wt) treated with tailored therapy 100% pts treated with non-tailored therapy

Personalisierte Medizin in der PraxisDr. Bernhard KirschbaumDVFA Life Science ConferenceFrankfurt, 17. Juni 2009

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Merck SeronoThe largest division of the Merck Group

PharmaceuticalsRevenues FY2008: €5,429m

Merck Serono€4,987m

Chemicals

Consumer Health Care€442m

Liquid Crystals

Cross-divisional functions / Central functions

Merck GroupRevenues FY2008: €7,558m

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v i s

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Business sectors

Performance & Life Science Chemicals

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Merck Serono –Key Facts & Figures

Established: January 5, 2007

Business: Innovative small molecules & biopharmaceuticals

Employees: >17,500

President: Elmar Schnee

Headquarters: Geneva, Switzerland

Key growth drivers:

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Research Development Market

Oncology

Endocrinology

* Currently in Development

Autoimmune & Inflammatory Diseases (AIID)

Fertility

Neurodegenerative diseases

Oncology

New Specialist TherapiesOsteoarthritis*, Rheumatology*, etc.

Neurodegenerative diseasesMultiple Sclerosis, Parkinson‘s*

Fertility

Endocrinology

CM Care & local products

Therapeutic Area Focus:From Research and Development to Market

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Stratified Medicine is about Stratified Medicine is about adapting the treatmentadapting the treatment (molecule, dose, (molecule, dose, schedule,schedule,……) according to the patient) according to the patient’’s characteristics s characteristics

for better efficacy and less adverse events.for better efficacy and less adverse events.

Stratified Medicine: Definition

Personalized Medicine versus Stratified MedicinePatient sub-populationsIndividual patients,

e.g. cancer vaccine made from the patient’s tumor

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Stratified Medicine: Basic Principle

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How Can Stratified Medicine Help the Patients, Clinicians and Healthcare Systems?

Clinicians:• Therapy adjustment based on

disease and patient characteristics• Tool to optimize dosing

Patients:• More effective & predictive

treatment options

Healthcare Systems:• Better return on healthcare expenditure• More innovation through products with higher medical value using combination of

Diagnostics (Dx) and Pharma (Rx)

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Stratified Medicine as a Means to ContainHealth Care Expenditures

• Senator Obama introducesGenomics and PersonalizedMedicine Act (2006)

• President Obama’s economicalstimulus bill allocates US$1.1bn for comparative effectivenessresearch (2009)

Source: www.whitehouse.gov

Early identification of non responders has double value for the authorities – increasing pressure is expected:

• Increased patient benefit• Heath care cost containment

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Stratified Medicine and Pharma Business –New Opportunities / Added Complexity

Improvedbenefit / risk

ratio

Opens doors tonew indications

Higher & fastermarket

penetration

Better price andreimbursement

Faster, more directed

development

Smallertarget market

HigherR&D costs

Complication through

Dx testingIn practice

BusinessBusinessOutcomeOutcome+

-

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Merck Serono Pipelineas per April 27, 2009

Phase IIIPhase IIPhase I

ARX 201Growth hormone deficiencies

NHS-IL2-LTSolid tumors

DI17E6Solid tumors

Eg 5 inhibitorSolid tumors and hematologicalmalignancies

IMO-2055, TLR9 immunomodulator, Solid tumors

Survivac Cancer VaccineSolid tumors

Fibroblast Growth Factor 18Osteoarthritis

Aurora Kinase Inhibitor AS703569Solid tumors and hematologicalmalignancies

Adecatumumab (MT201)Colorectal Cancer

Tucotuzumab celmoleukin(EMD 273066/huKS-IL2), Small cell lung cancer (SCLC)

EMD 273063 (hu14.18-IL2),immunocytokinePediatric neuroblastoma

Hyperglycosylated FSHInfertility (ART)

EMD 273063 (hu14.18-IL2),immunocytokineMelanoma

AtaciceptRheumatoid Arthritis

Erbitux® (cetuximab)Breast cancer

AtaciceptMultiple Sclerosis

Erbitux® (cetuximab)Adj Colon Cancer

Erbitux® (cetuximab)Gastric Cancer

SafinamideEarly stage Parkinson’s

AtaciceptLupus

CilengitideGlioblastoma

Stimuvax®

NSCLC

SafinamideMid-to-late stage Parkinson’s

Rebif New Formulation in CIS (REFLEX)Cladribine tablets Relapsing forms of MS

in RegistrationPhase IIIPhase IIPhase I

TesamorelinHIV patients with lipodystrophy(US only)

Rebif New Formulation Relapsing forms of MSFDA: Submission filed

MEK InhibitorSolid tumors

Cladribine tablets in CIS

CilengitideSCCHN

Sonepcizumab (ASONEPTM)Solid tumors

Erbitux® (cetuximab)NSCLC1st line therapyEMEA: Submission filed

CilengitideNSCLC




DI17E6Solid tumors

















AtaciceptLupus


Stimuvax®

NSCLC








CilengitideSCCHN



CilengitideNSCLC

OncologyNeurodegenerative DiseasesAutoimmune & Inflammatory DiseasesFertilityEndocrinology

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DI17E6Solid tumors

















AtaciceptLupus


Stimuvax®

NSCLC








CilengitideSCCHN



CilengitideNSCLC




DI17E6Solid tumors

















AtaciceptLupus


Stimuvax®

NSCLC








CilengitideSCCHN



CilengitideNSCLC

Biomarker and or stratification activities

OncologyNeurodegenerative DiseasesAutoimmune & Inflammatory DiseasesFertilityEndocrinology

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Merck Serono Pipelineas per April 27, 2009

Stratification is an important part of the Merck Serono strategy.Over 60% of our portfolio include Biomarker programs

(predictive, mechanistic, surrogates).

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Stratified Medicine: A Reality at Merck Serono

• KRAS stratification for Erbitux® was key to therapeutic expansion.

• Two stratified Phase III programs ongoing in Oncology – Cilengitideand Stimuvax

• Implementation of stratified medicine approach across the whole development portfolio

• Mandatory search for stratification biomarkers in our discovery process.

• Creation of a specialized function dedicated to stratified medicine.

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KRAS as a Predictive Marker for Erbitux® Efficacy in Metastatic Colorectal Cancer (mCRC)

KRAS patient status influences the efficacy of Erbitux®

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Months12 14

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Months80 2 4 6 10 1612 14

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Months80 2 4 6 10 1612 14

Cetuximab + FOLFIRI FOLFIRI

KRAS wild-type

KRAS wild-type

KRAS mutant KRAS mutant

Chemotherapy (FOLFIRI) +/- Cetuximab in first line treatment of mCRC

65% of patients

65% of patients

35% of patients35% of patients

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Improving tumor responses in mCRC: impact of tailored therapy and patient selection

ITT, intent-to-treat population; wt, wild-type; LLD, liver-limited disease

1. Folprecht et al. ESMO 2008; 2. Van Cutsem et al. ESMO 2008; 3. Bokemeyer et al. ASCO 2008; 4. Van Cutsem et al. ASCO 2008; 5. Saltz et al. WCGIC 2007

Personalized / tailored therapy– a new era in mCRC

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Benefit-effort ratio

100% pts treated with non-tailored therapyIdentified 60% pts (KRAS wt) treated with tailored therapy

Target specific patient group (KRAS wt) No indicators to select patients

Maximize success in clinical studiesGood clinical benefit in stratified patients Avoid unnecessary adverse effectsEfficient from health economics perspective

Variable success in clinical studiesVariable clinical benefit in allcomersRisk of unnecessary adverse effectsInefficient from health economics perspective

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Extension of mCRC Indication to 1st Line withKRAS Stratification

11stst lineline74,200 patients74,200 patients

22ndnd lineline32,200 patients32,200 patients

33rdrd lineline10,200 patients10,200 patients

Treatment duration

32 weeks20 weeks16 weeks

KRAS wild-type48,230 patients

KRAS wild-type 20,930 patients

KRAS wild-type6,630 patients

KRAS wild-type65%

*Data for biggest 5 countries in Europe, Source: OncFoundation2007 projections for 2008

Treating 2nd and 3rd line,both KRAS wild-type and mutant:Market = 807,200 weeks treatment

Treating 1st line,KRAS wild-type only:

Market = 1,543,360 weeks treatment

TreatmentTreatmentlineline

Bigger market enabled by stratificationHigher penetration due to improved efficacy

KRAS mutant25,970 patients

KRAS mutant 11.270 patients

KRAS mutant3,570 patients

KRAS mutant35%

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1 June 2009: Breakthrough for Erbitux in the UK ─ NICE recommendation thanks to KRAS

85 pieces of coverage for NICE (11 in major newspapers/newswires)

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Cilengitide in Glioblastoma

• Glioblastoma is a rare tumor, difficult to treat.

• The methylation of the MGMT* gene promoter is a potential stratification marker.

• Increased likelihood to succeed in Phase III using MGMT stratification.

Stratified medicine helps to meet unmet medical needs and to access additional indications

*O-Methylguanine-DNA Methyltransferase

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Study Conduct & BM Logistics

Biomarker Technologies

Consequences of Stratified Medicine Implementation on Technology ManagementNew capabilities → New complexities

Drug Development

Clinical Study Design

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Implementation of Stratified Medicine Has a Strong Impact on Drug Development Process

• Early integration in discovery and development process is important• Good early PK/PD research is essential• Competitive advantage to learn the lessons early

DiscoveryDiscovery PreclinicalPreclinicalDevelopmentDevelopment Phase IPhase I Phase IIPhase II Phase IIIPhase III

RegulatoryRegulatoryApprovalApprovalLaunchLaunch

• Identification of stratification• Validation of marker assay

• Label consideration based on marker status

• Analytical validation of diagnostic kit

• Clinical utility assessment for stratification• Design clinical trials

• Clinical validation of diagnostic kit

• Label consideration based on trial

• Address regulatory requests

• Ensure properlogstics

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Requirements for Stratification Kits in the Pharma Business

• Technical reliability:– Selective– Sensitive– Reproducible– Validated in clinical setting– Short turn-around

• Market access:– Properly distributed– Technically user-friendly– Financially affordable

Conditions for Conditions for ““good stratification kitsgood stratification kits””from the Rx standpoints:from the Rx standpoints:

Alignment of Rx and Dx is important

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Are the Current Rx/Dx Business ModelsChallenged in the Context of Stratified Medicine?

• Price is set according to the medical value

Innovative drugs increasing the response rate - bringing real added benefit to the patients - will enjoy higher reimbursement

• Price is set according to the product cost

Innovative genotyping kit increasing the response rate will be reimbursed at the level of other genotyping methods

Will Dx benefit increasingly from value-based recognition?

Rx reimbursement:Value-based system

Dx reimbursement:Cost-based system

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Dx and Rx Interactions

• Dx develops stratification markers for marketed drugs without Rx partnership

• Strong impact on Rx business since drug price is unlikely to be re-negotiable

• Kit development risk shouldered by Dx

• Risk of double marginalization

• Dx/Rx misalignment might be detrimental for patients benefit

• Dx co-develops stratification markers with Rx

• Higher Dx price negotiable at launch

• Shared development risk, mainly covered by Rx

• Profit sharing & optimization

• Aligned commercialization efforts -Best medical benefit for patients

Stratified Medicine might result in a new Dx/Rx symbiosis.

Invasive model Collaborative model

Two extreme models:

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From Complexity to Oversimplification & Back to Complexity

Genomics Era

Post-GenomicsEra

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Contact information

Dr. Thomas Kornek℡ +49 6151 72-7434Claudia Nickolaus℡ +49 6151 72-2584Alessandra HeinzAssistant Investor Relations℡ +49 6151 72-3321

Merck KGaAInvestor RelationsFrankfurter Str. 25064293 DarmstadtGermanyFax: +49 6151 [email protected]

Thank you for yourkind attention!

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Personalisierte Medizin in der Praxis - DVFA · Erbitux ® (cetuximab) Breast ... Identified 60% pts (KRAS wt) treated with tailored therapy 100% pts treated with non-tailored therapy