pioneering personalized medicine through partnering · pioneering personalized medicine through...
TRANSCRIPT
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Pioneering Personalized Medicine
through Partnering
Jörg Teubner
Marketing Manager Personalized Healthcare, QIAGEN
November 19, 2011
Personalized MedicineDefinition
Definition of Personalized Medicine:
Personalized Medicine is the use of information about a
person's genes, proteins and environment to prevent and
treat disease.
Molecular assays measuring levels of proteins, genes or
specific mutations deliver the neccessary results to provide a
specific therapy for an individual's condition by stratifying
disease status, selecting the proper medication and
tailoring drug dosages to a particular patient's specific
condition and needs.
The challenge: Selection of the suitable drug
Valuable drugs go to unsusceptible patients
Source: Brian B. Spear, Margo Heath-Chiozzi, Jeffrey Huff, “Clinical Trends in Molecular Medicine, Volume 7, Issue 5, 1 May 2001, Pages 201-204
Anti-Depressants
Asthma
Diabetes
Arthritis
Alzheimer
Cancer
62%
60%
57%
50%
30%
25%
Drug Efficacy
= Drug does not work
.A specific drug works in some
patients, in some not.
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IPASS (IRESSA Pan-ASia Study): randomised, parallel-group study to assess the efficacy, safety and tolerability
of gefitinib (novel drug) versus carboplatin/paclitaxel (standard therapy) as first line treatment in a clinically
selected patient population from Asia.
IPASS Study
Sample & Assay Technologies
Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma.
TS. Mok, Y-L. Wu, S. Thongprasert, C-H. Yang, D-T. Chu, N, Saijo, et al., NEJM, Sep 2009; 361: 947-957.
Example: Non-small cell lung carcinoma (NSCLC)
Drug efficacy correlates with EGFR mutation status
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"Routine use of KRAS mutational testing in colorectal cancer patients could save the
health care system more than $600 million in drug costs alone."
Example: metastatic Colorectal carcinoma (mCRC)
Drug efficacy correlates with KRAS mutation status
KRAS mutation negativeKRAS mutation positive
Panitumumab+BSC
Best Supportive Care
(BSC)
Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer.
R.G. Amado, M. Wolf, M. Peeters, et al., Journal of Clinical Oncology, Vol 26, (10), 2008: pp. 1626-1634
Clinical trial demonstrating that patients with a wild type KRAS gene in DNA from colorectal cancer cells,
showed significant benefit to treatment with Panitumumab (“Vectibix”). Patients whose tumor contained
mutated KRAS gene had no drug response.
Panitumumab+BSC
Best Supportive Care
(BSC)
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Pathology today and tomorrow
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Pioneering Personalized Medicine through Partnering
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Complex
sample
Sample and Assay Technologies
1Sample
Technologies2
Pure
Analyte3
Assay
Technologies4
Target Detected
Golgi apparatus, Glycoproteins, Microtubules, Mitochondria, Mitochondrial
nucleic acids, Vacuoles, Talin, Nucleolus, Polymerases, Ceramides,
Chromosomes, Chromatin, mRNA, Cytoplasm, Leucocytes, Sugars, Lipids,
Salts, Urea, Carbonic acids, Cofactors, Precursors, Hemoglobins,
Erythrocytes, Monocytes, Smooth endoplasmatic reticulum, Macrophages,
Thrombocytes, Platelets, Lymphocytes, Basophils, Eosinophils, Neutrophils,
Megacaryocytes, Plasma, Clotting factors, Actin, Microfilaments, Serum,
Fibrin, Lysosomes, Ezrin, DNA, Hemaglobins, Heptaglobins, Transferrin,
Fibrinogen, Serum albumin, tRNA, Salts, Polymerases, Centrioles,
Immunoglobulins, DNA,, Cytokines, Angiotensins, Chemokines, Bradykines,
Plasma membranes, Ribosomes, Actin, Vesicles, Complement components,
Nuclei, Rough endoplasmatic reticulum, Nucleoli, Golgi apparatus,
Glycoproteins, Microtubules, Mitochondria, Mitochondrial nucleic acids,
Vacuoles, Talin, Nucleolus, Polymerases, Ceramides, Chromosomes,
Chromatin, mRNA, Cytoplasm, Leucocytes, Sugars, Lipids, Salts, Urea,
Carbonic acids, Cofactors, Precursors, Hemoglobins, Erythrocytes,
Monocytes, Smooth endoplasmatic reticulum, Macrophages, Thrombocytes,
Platelets, Lymphocytes, Basophils, Eosinophils, Neutrophils,
Megacaryocytes, Plasma, Clotting factors, Actin, Microfilaments, Serum,
Fibrin, Lysosomes, Ezrin, Hemaglobins, Heptaglobins, Transferrin,
Fibrinogen, Serum albumin, tRNA, Carrier proteins
Golgi apparatus, Glycoproteins, Microtubules, Mitochondria, Mitochondrial
nucleic acids, Vacuoles, Talin, Nucleolus, Polymerases, Ceramides,
Chromosomes, Chromatin, mRNA, Cytoplasm, Leucocytes, Sugars, Lipids,
Salts, Urea, Carbonic acids, Cofactors, Precursors, Hemoglobins,
Erythrocytes, Monocytes, Smooth endoplasmatic reticulum, Macrophages,
Thrombocytes, Platelets, Lymphocytes, Basophils, Eosinophils, Neutrophils,
Megacaryocytes, Plasma, Clotting factors, Actin, Microfilaments, Serum,
Fibrin, Lysosomes, Ezrin, DNA, Hemaglobins, Heptaglobins, Transferrin,
Fibrinogen, Serum albumin, tRNA, Salts, Polymerases, Centrioles,
Immunoglobulins, DNA,, Cytokines, Angiotensins, Chemokines, Bradykines,
Plasma membranes, Ribosomes, Actin, Vesicles, Complement components,
Nuclei, Rough endoplasmatic reticulum, Nucleoli, Golgi apparatus,
Glycoproteins, Microtubules, Mitochondria, Mitochondrial nucleic acids,
Vacuoles, Talin, Nucleolus, Polymerases, Ceramides, Chromosomes,
Chromatin, mRNA, Cytoplasm, Leucocytes, Sugars, Lipids, Salts, Urea,
Carbonic acids, Cofactors, Precursors, Hemoglobins, Erythrocytes,
Monocytes, Smooth endoplasmatic reticulum, Macrophages, Thrombocytes,
Platelets, Lymphocytes, Basophils, Eosinophils, Neutrophils,
Megacaryocytes, Plasma, Clotting factors, Actin, Microfilaments, Serum,
Fibrin, Lysosomes, Ezrin, Hemaglobins, Heptaglobins, Transferrin,
Fibrinogen, Serum albumin, tRNA, Carrier proteins
DNA Information
ASSAY
Technologies
SAMPLE
Technologies
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therascreenFully validated workflows
Diagnostic ResultsPatient
sampleSample technologies Assay technologies
Sample
PAXgene
Tissue
“Classical”
FFPE TissueAutomated: QS-RGQ
Manual: QIAamp (eg. DNA FFPE)
RotorGene-Q
PyroMark Q24
Comprehensive&
Complex Tasks
Selective &
Sensitive Tasks
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therascreen
Reliability
Regulatory status (CE-IVD)
Workflow solutions
Short Turn around time
ARMS Scorpions qPCR
Highest Sensitivity on the
market
Selective mutation detection
Ease of use
One-step procedure
Pyrosequencing
Comprehensive results in
real-time
Complex mutation testing
with simple data interpretation
Small amount of starting material
therascreen
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therascreen RGQ PCR workflow
~ 140main ~ 15 min~ 2,5 h
DNA purificationDNA
Assessment
Result
Interpretation
Mutation
Testing
therascreen (RGQ)
PCR Kits
Rotor-Gene Q Analysis Software
The PCR procedure takes less than 3h.
QIAamp DNA FFPE
Tissue Kit (56404)
“optional”
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Features of the therascreen PCR portfolio
QIAGEN Bidirectional DNA
Sequencing
Lower Limit of Detection <1% 25-30%
Analytical Sensitivity 100% 70-75%
Amplicon Size ~100bp 200bp
Procedure time (ex DNA extn) <3h 11h
Complexity Low High
Result Output Objective Subjective
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Pyrosequencing workflow
~ 2h ~ 10-60 min~ 15 min
DNA purification PCR PyrosequencingSample prep
therascreen Pyro
Kits
PyroMark Q24
Vacuum Prep Workstation
PyroMark Q24
PyroMark Q96ID
PyroMark Q96MD
Pyrosequencing provides quantitative results in a sequence context
in as little as 1 hour after PCR
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Features of the therascreen Pyro portfolio
therascreen Pyro KitsBidirectional
DNA Sequencing
TAT ~ 3h 11h
Regulatory Status CE-IVD marked assays n.a.
Information output Sequencing data Sequencing data
Starting materialHighly fragmented DNA in small
amounts (<10ng per reaction)
DNA shouldn’t
be too bad in
quality
Workflow SolutionWorkflow validation – from
Sample to Result– – –
Robustness +++ +
Result interpretation“one-click” result – easy
interpretation
Quite complex
and time
consuming
Sensitivity ~ 5% ~ 25% and more
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therascreen Pyro Kits
Specification Assay Design Mutations
KRAS Prescription of Erbitux & Vectibix in mCRC
patients, only when KRAS wt is present in the
cells
2 PCR + 2
Sequencing rxn
Plug-in
G12A G12D G12S G12V G12R
G12C G13D
Q61H Q61E Q61L
EGFR Detection of mutations & deletions in E18 –
E21. Important for Iressa and Tarceva in
mNSCLC first line therapy
4 PCR + 5
Sequencing rxn
Plug-in
G719S G719A G719C S768I
T790M L858R L861Q L861R
Deletions (20 most common ones)
BRAF Mutations in the BRAF occur mainly in
Melanoma (Zelboraf (Vemurafinib)
2 PCR + 2
Sequencing rxn
Reverse assay
V600E G464V G469A
V600M G464E G469V
V600A G466V G469E
V600G G466E
NRAS Mutations in NRAS codon 12, 13 & 61
metastatic colorectal cancer (mCRC) &
melanoma tumors
2 PCR + 2
Sequencing rxn
G12D G12S G12C G12V G12A
G12R G13D G13R G13V G13C
G13A G13S Q61L
Q61P Q61E Q61R Q61K Q61H
MGMT
“MBA”
Involved in repairing alkylated DNA.
Inactivation of the MGMT-gene leads to tumor
formation
1 PCR + 1
Sequencing rxn
48 rxn Kit !
4 CpG sites
UGT1A1
“MBA”
Only commercial assay on the market that can
detect var *6 & var *28 in the UGT1A1 gene
2 PCR + 2
Sequencing rxn
*6 = Gly Arg
*28 = 6 7 TA repeats
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Pioneering Personalized Medicine through Partnering
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Patient flowBased on NSCLC/EGFR testing
Origination
Primary Care
Evaluation
Specialist
Evaluation
Diagnosis
1st Line
Treatment
Fulfilment,
Adherence,
Re-evaluation
Maintenacne
Treatment
2nd Line Tx
3rd Line Tx
Patient
classification
Pathologist
Pathologist
Oncologist
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Conferences and educational events
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Pioneering Personalized Medicine through Partnering
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The CDx roadmap - stages in the life of a CDx
Used by pharma on
clinical trial patients
Development and
Regulatory Expertise
Used by diagnostic
labs on samples of
„real“ patients
Platform and product
distribution and marketing
Identify BiomarkersDevelop
Approved CDxSell CDxBiomarker
Discovery
Tools for Biomarker
Selection
Used by pharma on
preclinical and clinical
samples
Used by pharma on
model systems (cell-
lines)
Tools for Biomarker
Discovery
Drug development
Phase I and II
Drug development
Phase II and III Sell Drugs
Drug discovery
Pharma R&D
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TOMTOVOK™
Zelboraf
BKM120
QIAGEN partners:
and many more ...
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Your benefit: kits detecting clinical relevant mutations
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Pioneering Personalized Medicine through Partnering
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mCRC patients
11.250
new patients / year
~ 44.000€
per patient
KRAS testing for all patients
300€/patient
= 3,4M€Panitumumabtreatment incl. testing
35.6%
of all patients carry
KRAS mutations
Panitumumab for wtKRAS
368,3M€
Total costs
493M€
Total savings
121,3M€
each year
Total costs
371,7M€
Panitumumabtreatment w/o testing
Cost-EffectivenessCost saving-example for KRAS testing in mCRC (Turkey)
Source: based on GICS 2009: Huge cost savings from KRAS testing in Metastatic Colorectal Cancer, http://globocan.iarc.fr/ and Gelbe Liste 2011
+
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Pioneering Personalized Medicine through Partnering
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Pioneering Personalized Medicine through Partnering
Thanky you very much for your attention