Transcript Personalized Medicine - College of American Pathologists

TRANSFORMING PATHOLOGY:
Emerging technology driving practice innovation
Personalized Medicine &
Pathology
Friend or Foe?
Mara G. Aspinall
CAP Foundation
Chicago, Illinois
June 7, 2008
Personalized Medicine
- Friend or Foe?
 What is it?
 Why now?
 When will it be real?
 Call to Action for Pathologists
Personalized Medicine
Old Paradigm: Trial and Error Medicine
Successful When it Leads to
Innovation and Improves
Standard of Care.
Fails When We Settle for
“Trial and Error” Medicine
AS the Standard of Care.
Personalized Medicine
New Paradigm: Personalized Medicine
Linking Tests to Action and Therapy
Observation
Test
Action
Predictable
Response
Breaking The Cycle of Trial and Error Medicine
Personalized Medicine
Why is it Important?
Diagnosis Save Lives
Diagnosis Save Money
Personalized Medicine Test Categories
Drug Selection
Breast Cancer
Herceptin®
HER2
Drug Dosage
Colorectal Cancer
Camptosar®
UGT1A1
Drug Efficacy
Chronic Myelogenous Leukemia
Gleevec®
Quant BCR-ABL
Disease Status
Chronic Lymphocytic Leukemia
Campath®
Minimal Residual Disease
Recurrence Risk
Breast Cancer
Oncotype DX®
Multivariate Analysis
Predisposition
Breast Cancer
BRACAnalysis®
Gene sequencing, risk analysis
Personalized Medicine Saves Lives
100
Years Ago
80
Years Ago
60
Years Ago
5 Year
Survival
“Disease of the Blood”
Leukemia or Lymphoma
Chronic Leukemia
Acute Leukemia
Preleukemia
Today
~ 0%
Indolent Lymphoma
Aggressive Lymphoma
38 Leukemia types identified:
51 Lymphomas identified:
Acute myeloid leukemia (12 types)
Mature B-cell lymphomas (14 types)
Acute lymphoblastic leukemia (2 types)
Mature T-cell lymphomas (15 types)
Acute promyelocytic leukemia (2 types)
Plasma cell neoplasm (3 types)
Acute monocytic leukemia (2 types)
Immature (precursor) lymphomas (2 types)
Acute erythroid leukemia (2 types)
Hodgkin’s lymphoma (5 types)
Acute megakaryoblastic leukemia
Immunodeficiency associated lymphomas (5 types)
Acute myelomonocytic leukemia (2 types)
Other hematolymphoid neoplasms (7 types)
Chronic myeloid leukemia
Chronic myeloproliferative disorders (5 types)
Myelodysplastic syndromes (6 types)
Mixed myeloproliferative/myelodysplastic syndromes (3 types)
70%
Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, Mariotto A, Feuer EJ, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2002, National Cancer
Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2002/, based on Nov 2004 SEER data submission, posted to
the SEER web site 2005.
Molecular Characterization
Standard Practice In Hematologic Oncology
Morphology Evaluation
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Fluorescence-Activated Cell Sorting
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Cytogenetic Analysis
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Molecular Analysis
Expanded Characterization
and Response Prediction
Identification of t(15;17) translocation in AML patients leads to specific treatment (ATRA)
which changed the overall survival from 0% 40 years ago to 80% now
Personalized Medicine Reduces
Ineffective Treatment in Colon Cancer
Do Not Treat
kras Testing
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Treat with Erbitux
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Langreth, R. (2008), ‘Imclone’s Gene Test Battle’, Forbes.com, 16May
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Treat with Erbitux
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Treatment
Success
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Personalized Medicine is Cost Effective in
Treatment of Colon Cancer
Erbitux Treatment Cost Comparisons with and without
kras Testing to Direct Personalized Treatment
$200,000
$156,554
 60% reduction in cost
per success
$150,000
$97,022
$100,000
$50,000
$22,800
side effects from
ineffective treatment
$38,000
$0
Average Treatment Cost (per
person)
With kras Testing
 40% of patients spared
Average Treatment Cost (per
success)
Without kras Testing
 Overall success rate is
unchanged at 25%
Langreth, R. (2008), ‘Imclone’s Gene Test Battle’, Forbes.com, 16May
Personalized Medicine is Beneficial in
Treatment of Pancreatic Cancer
Suspected
Pancreatic
Cancer
Watch And
Wait
Increased
Risk
Pancreatectomy
Insulin
Insufficiency
Two
Bad
Choices
30% Pancreatic Cancer
Suspected
Pancreatic
Cancer
Treat Aggressively
PathFinderTG
Diagnostic
Informed
Choices
70%
Benign Condition
Do Nothing
Rina Wolf Testimony before House Committee on Small Business, Subcommittee on Regulations, Healthcare and Trade, May 14, 2008
Patients Don’t Have Time for Trial & Error
Disease
1 Year
Survival
Lung cancer
42%
Colorectal cancer
76%
Chronic myeloid leukemia (CML)
63%
93%
Heart failure
74%
End stage renal disease
78%
2007 USRDS Annual Data Report Levy, et. al., Long-term trends in the incidence and survival from heart failure, NEJM, 2002; 347(18):1397-402
CancerMpact, MattsonJack; NCI SEER data, average across all stages at Dx
Personalized Medicine
- Friend or Foe?
 What is it?
 Why now?
 When will it be real?
 Call to Action
Why Now?
The Human Genome Project
Why Now?
Explosion of the “Omics”
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Proteomics
Allergenomics
Bibliomics
Biomics
Cardiogenomics
Cellomics
Chemogenomics
Chemoproteomics
Chromatinomics
Chromonomics
Chromosomics
Combinatorial Peptidomics
Computational RNomics
Cryobionomics
http://www.genomicglossaries.com
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Crystallomics
Cytochromics
Cytomics
Degradomics
Ecotoxicogenomics
Eicosanomics
Embryogenomics
Enviromics
Epigenomics
Epitomics
Expressomics
Fluxomics
Fragmentomics
Fragonomics
Etc…
Why Now?
Diagnostic Technology Has Improved
Past – Macro Level Testing
Tests differentiated disease from non-disease
Disease defined by location and size
Today – Molecular Level Testing
Disease defined by individual biology and /or
DNA of tumor or virus
Tests to subcategorize disease:
predict outcomes of specific therapeutic
screen for adverse events
monitor disease
Why Now?
Diagnostic Technology Has Improved
Tomorrow – Predictive Testing
Multiple technology platforms needed for higher
analytic validity
Multi-factorial testing for common, complex
diseases
Multi-gene signatures as standard for cancer
New Sample Types –
Urine, Saliva, Breath, others?
Increased Use of Diagnostic Imaging
Why Now:
Increased Government Interest
 FDA
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In-vitro Diagnostic Multivariate Index Assay
(IVD MIA) Draft Guidance
Pharmacogenomics voluntary data submission
 HHS Secretary’s Committee on Genetics,
Health and Society (SACGHS)
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Report recommending filling gaps in oversight of
genetic tests
 President’s Council on Science and Technology
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Upcoming Report of Personalized Medicine
Personalized Medicine
- Friend or Foe?
 What is it?
 Why now?
 When will it be real?
 Call to Action for Pathologists
The Personalized Medicine Timeline
Fear
Value
Acceptance
The Personalized Medicine Timeline
Fear
Payers:
Adds to My Cost Without Return
Treating Physicians: Too Prescriptive for Me
Patients: Will I Be Denied Access to New Drugs?
Regulators: How Do We Handle New Complexities?
Diagnostics: More Tests With Poor Reimbursement
Pharma: Reduces My Market
Pathologists: Reduces My Market
Pharma Fear
Spending Up but New Drug Approvals Not
60
New Drug Approvals
45
PhRMA R&D Spending
40
50
35
40
30
25
30
20
20
15
10
10
5
0
0
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Pharmaceutical Research and Manufactures of America: Pharmaceutical Industry Profile 2006
www.fda.gof/oc/initiatives/criticalpath/whitepaper.html
Pharma Fear
Blockbusters Going Off Patent
• 105 blockbuster drugs with $237 billion in sales
• 37 % of all prescription pharmaceutical sales
• 7 of the top 10 drug launches in 2006 were generics
$ Billion
$21
$21
$17
$15
$13
$12
$9
2006
2007
2008
2009
2010
2011
2012
Big Pharma Faces Grim Prognosis, Wall Street Journal, 12/06/2007
Cowen and Company
Pharma Fear (and Opportunity)
Drug Efficacy is Too Low
Therapeutic Area
Oncology
Alzheimer's
Incontinence
Hepatitis C virus
Osteoporosis
Rheumatoid arthritis
Migrane
Effective Rate (%)
25%
30%
40%
47%
48%
50%
51%
Cardiac Arrythmias
60%
Asthma
60%
Spears et al. TRENDS in Molecular
Medicine Vol. 7 No. 5 May 2001
Pharma Fear (and Opportunity)
Adverse Events are Too High
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2.2 Million People Impacted Annually
$177 billion annual cost
Single largest cause of drug market withdrawals
Cause Of Death
Number Of Deaths
Heart Disease
652,091
Malignant Neoplasms
559,312
Cerebrovascular Disease
143,579
Lower Respitory Disease
130,933
Accidents
117,809
Adverse Drug Reactions
106,000
National Vital Statistics Reports, Vol. 56, No. 10, March 7, 2008, 2001United States Data
Pharma Fear (and Opportunity)
Prescription Compliance is Too Low
Takes Medication
as Prescribed
25%
Stops before
completed
29%
Fills but Does not
Take
12%
Does not Fill
12%
Takes less than
Prescribed
22%
Source: American Heart Association
Pharma Fear (and Opportunity)
Drug Reimbursement System Changing?
• Reimbursement ONLY if patient benefits from drug
• REFUND if patient does not benefit after treatment
• Current Examples:
• Velcade for multiple myeloma
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Johnson & Johnson and Government Payors in UK and France
Full refund to payor if patient does not achieve 50% biomarker reduction
Oncotype DX
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Genomic Health and United Healthcare
Price adjusted if tests do not show change in clinical practice
Pricing Pills by the Results, New York Times, July 14, 2007
Velcade For Multiple Myeloma
• Protocol
• Patient is treated with a maximum of 4 cycles of treatment
($24,800 US)
• Serum M protein, a biomarker for tumor load, is monitored with
blood or urine test
Electrophoresis: Normal plasma
Serum M protein
www.nytimes.com/2007/07/14/business/14drugprice.html?_r=1&oref=slogin
Nature Reviews, Drug Discover: December 2007, v 6, p 945
www.nice.org.uk/nicemedia/pdf/MyelomaDofHSummaryResponderScheme.pdf
Velcade For Multiple Myeloma
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Biomarker is linked to drug efficacy
Biomarker results are then linked to payment
• Complete response (CR): minimal / no serum M protein
- PAID
• Partial response (PR): > 50 % reduction of serum M
protein – PAID
• Minor or Minimal response (MR): < 50 % reduction of
serum M protein - REFUND
www.nytimes.com/2007/07/14/business/14drugprice.html?_r=1&oref=slogin
Nature Reviews, Drug Discover: December 2007, v 6, p 945
www.nice.org.uk/nicemedia/pdf/MyelomaDofHSummaryResponderScheme.pdf
Pathologist Fear?
New Sample Types Beyond Tissue
• Molecular Blood Tests
• Breath Tests
• Urine Tests
Pathologist Fear?
New Technology Trumps Morphology
Currently, 17 % of Burkitt Lymphoma are incorrectly
diagnosed as Diffuse Large B Cell Lymphoma
Classic
Burkitt Lymphoma
Atypical
Burkitt Lymphoma
Diffuse Large
B Cell Lymphoma
Source: Louis Staudt, MD, PhD. National Cancer Institute
Pathologist Fear?
New Technology Beyond Morphology
Diffuse Large
Burkitt
Gene Expression
Differentiates
Burkitt Lymphoma from
B-cell
Lymphoma
Lymphoma
Diffuse
Large B Cell Lymphoma, Improving Patient Care
Louis Staudt, MD, PhD,
National Cancer Institute
Pathologist Fear?
Molecular Tests are Exploding
Number
IVD-MIA Devices
200
200
100
6
0
Today
In-Development
Source: In Development – Coalition for 21st Century Medicine Survey 2007
Venture Capital is focused on DX
Increased Venture Capital Spending
$ (Millions)
$500
$400
$300
$200
$100
$409
$387
2006
2007
$297
$120
$170
$160
$184
2002
2003
2004
$2001
Year
2005
Nature Biotechnology Volume 24
Number 8 August 2006,
BioCentury's BCIQ,
Genzyme Analysis
Pharma and Pathologist
Fear and Opportunity
FDA Stance On Valid Genomic Biomarkers
In The Context of Approved Drug Labels
 Drugs with Labels Containing Pharmacogenomic
Information – 121
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Drugs with Tests Required - 2
Drugs with Tests Recommended - 3
Drugs with Tests for Information Only – 16
Drugs with No Test Mentioned – 100
Clinical Ligand Assay Society 32nd International Meeting Louisville, KY May 22, 2006
Felix W. Frueh, PhD Associate Director for Genomics, Office of Clinical Pharmacology CDER/FDA
Personalized Medicine
- Friend or Foe?
 What is it?
 Why now?
 When will it be real?
 Call to Action
Call to Action
Need to Capture the Future
Present
Future
Morphology Tests
Molecular Tests
Stable Base of Technology
Many New Emerging Technologies – including
Microarrays
Single Gene Tests
Multi Gene / Multi Technology Tests
Tissue Samples
Multiple Sample Types
Timeframe Varies and Controlled by Pathologist
Point of Care Diagnosis Desired
(IVD kits more available)
Pathologist Initiates& Interprets Diagnosis
Molecular Lab Provides Diagnosis directly to
Treating Physician
Call to Action
Friend or Foe?
Personalized Medicine Needs to be a Friend
Pathologists Need to :
- Own Personalized Medicine
- Source of expertise on all tests available
- Interpreter and consolidator of all test results
- Educator of all other physicians on diagnosis
Move Industry from Fear to Acceptance
Moving From Fear To Acceptance
 Physician Education
 Data – Integration into the EHR / EMR
 Policy – Reimbursement and Regulatory
Aspinall and Hamermesh, Harvard Business Review, Oct 2007
Move From Fear to Acceptance
 Physician Education
 Build commitment through education for community physicians
 Publish new PM practice guidelines – tests and technologies
 Data & Integration into EHR
 Create Convincing Data on the positive outcomes and health
economics of appropriate use of PM diagnostics
 Leadership in the build of the EHR / EMR
 Policies Needed
 Reimbursement based on value rather than activity
 Regulatory options that encourage diagnostic and drug
combinations
 Embrace “Era of Diagnostics” For Improved Outcomes
Move From Fear to Acceptance
 Physician Education – PATHOLOGIST LEAD
 Build commitment through education for community physicians
 Publish new PM practice guidelines – tests and technologies
 Data & Integration into EHR – PATHOLOGIST LEAD
 Create Convincing Data on the positive outcomes and health
economics of appropriate use of PM diagnostics
 Leadership in the build of the EHR / EMR
 Policies Needed – PATHOLOGIST LEAD
 Reimbursement based on value rather than activity
 Regulatory options that encourage diagnostic and drug
combinations
 Embrace “Era of Diagnostics” For Improved Outcomes
Call to Action
Opportunities…
•
•
•
•
Expand scope of practice
Increase impact on patient treatment
Institutional Knowledge Coordinator
Cutting edge expertise
• Leadership in Personalized Medicine
– it is here to stay
Future Health Care Spending
Individual Health Care Spending Curve
Current
Practice
Improved
Quality of Life
&
Financial Savings
Health
Care
$
Potential of
Personalized
Medicine
Years
Source: Deloitte Development LLC 2006
Acknowledgements
 David Turnquist, Boston College
 Deloitte Center for Health Solutions
 Personalized Medicine Coalition
TRANSFORMING PATHOLOGY:
Emerging technology driving practice innovation