Personalized Medicine

1
TRANSFORMING PATHOLOGYEmerging technology
driving practice innovation
2
Personalized Medicine Pathology Friend or
Foe?

• Mara G. Aspinall
• CAP Foundation
• Chicago, Illinois
• June 7, 2008

3
Personalized Medicine- Friend or Foe?

• What is it?
• Why now?
• When will it be real?
• Call to Action for Pathologists

4
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.
5
Personalized Medicine
New Paradigm Personalized Medicine Linking
Tests to Action and Therapy
Predictable Response
Observation
Test
Action
Breaking The Cycle of Trial and Error Medicine
6
Personalized Medicine Why is it Important?

• Diagnosis Save Lives
• Diagnosis Save Money

7
Personalized Medicine Test Categories
Drug Selection Drug Selection Drug Selection Drug Selection Drug Selection
Breast Cancer Breast Cancer Breast Cancer Herceptin HER2
Drug Dosage Drug Dosage Drug Dosage Drug Dosage Drug Dosage
Colorectal Cancer Colorectal Cancer Camptosar Camptosar UGT1A1
Drug Efficacy Drug Efficacy Drug Efficacy Drug Efficacy Drug Efficacy
Chronic Myelogenous Leukemia Chronic Myelogenous Leukemia Gleevec Gleevec Quant BCR-ABL
Disease Status Disease Status Disease Status Disease Status Disease Status
Chronic Lymphocytic Leukemia Campath Campath Campath Minimal Residual Disease
Recurrence Risk Recurrence Risk Recurrence Risk
Breast Cancer Oncotype DX Oncotype DX Oncotype DX Multivariate Analysis
Predisposition Predisposition Predisposition
Breast Cancer BRACAnalysis BRACAnalysis BRACAnalysis Gene sequencing, risk analysis
8
Personalized Medicine Saves Lives
5 Year Survival
0
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.
9
Molecular CharacterizationStandard Practice In
Hematologic Oncology
Morphology Evaluation Fluorescence-Activated
Cell Sorting Cytogenetic Analysis Molecular
Analysis Expanded Characterization and
Response Prediction
Identification of t(1517) translocation in AML
patients leads to specific treatment (ATRA)
which changed the overall survival from 0 40
years ago to 80 now
10
Personalized Medicine Reduces Ineffective
Treatment in Colon Cancer
Do Not Treat
?
?
?
?
kras Testing
?
?
?
?
?
?
?
?
?
?
?
?
Treat with Erbitux
?
?
?
?
?
?
?
?
?
?
?
?
Treat with Erbitux
Treatment Success
?
?
?
?
?
?
?
?
?
?
?
?
?
?
?
Langreth, R. (2008), Imclones Gene Test
Battle, Forbes.com, 16May
11
Personalized Medicine is Cost Effective in
Treatment of Colon Cancer

• 60 reduction in cost per success
• 40 of patients spared side effects from
  ineffective treatment
• Overall success rate is unchanged at 25

Langreth, R. (2008), Imclones Gene Test
Battle, Forbes.com, 16May
12
Personalized Medicine is Beneficial in Treatment
of Pancreatic Cancer
Watch And Wait
Increased Risk
Two Bad Choices
Suspected Pancreatic Cancer
Pancreatectomy
Insulin Insufficiency
Pancreatic Cancer Treat Aggressively
30
Suspected Pancreatic Cancer
PathFinderTG Diagnostic
Informed Choices
Benign Condition Do Nothing
70
Rina Wolf Testimony before House Committee on
Small Business, Subcommittee on Regulations,
Healthcare and Trade, May 14, 2008
13
Patients Dont Have Time for Trial Error
Disease 1 Year Survival
Lung cancer 42
Colorectal cancer 76
Chronic myeloid leukemia (CML) 63
Heart failure 74
End stage renal disease 78
93
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
14
Personalized Medicine- Friend or Foe?

• What is it?
• Why now?
• When will it be real?
• Call to Action

15
Why Now? The Human Genome Project
16
Why Now? Explosion of the Omics

• Proteomics
• Allergenomics
• Bibliomics
• Biomics
• Cardiogenomics
• Cellomics
• Chemogenomics
• Chemoproteomics
• Chromatinomics
• Chromonomics
• Chromosomics
• Combinatorial Peptidomics
• Computational RNomics
• Cryobionomics

• Crystallomics
• Cytochromics
• Cytomics
• Degradomics
• Ecotoxicogenomics
• Eicosanomics
• Embryogenomics
• Enviromics
• Epigenomics
• Epitomics
• Expressomics
• Fluxomics
• Fragmentomics
• Fragonomics
• Etc

http//www.genomicglossaries.com
17
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

18
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

19
Why Now Increased Government Interest

• FDA
• In-vitro Diagnostic Multivariate Index Assay
  (IVD MIA) Draft Guidance
• Pharmacogenomics voluntary data submission
• HHS Secretarys Committee on Genetics, Health and
  Society (SACGHS)
• Report recommending filling gaps in oversight of
  genetic tests
• Presidents Council on Science and Technology
• Upcoming Report of Personalized Medicine

20
Personalized Medicine- Friend or Foe?

• What is it?
• Why now?
• When will it be real?
• Call to Action for Pathologists

21
The Personalized Medicine Timeline
Value
Fear
Acceptance
22
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
23
Pharma FearSpending Up but New Drug Approvals Not
Pharmaceutical Research and Manufactures of
America Pharmaceutical Industry Profile
2006 www.fda.gof/oc/initiatives/criticalpath/white
paper.html
24
Pharma FearBlockbusters 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

Big Pharma Faces Grim Prognosis, Wall Street
Journal, 12/06/2007 Cowen and Company
25
Pharma Fear (and Opportunity) Drug Efficacy is
Too Low
Therapeutic Area Effective Rate ()
25
Spears et al. TRENDS in Molecular Medicine Vol. 7
No. 5 May 2001
26
Pharma Fear (and Opportunity) Adverse Events are
Too High

• 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
27
Pharma Fear (and Opportunity)Prescription
Compliance is Too Low
Source American Heart Association
28
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
• Johnson Johnson and Government Payors in UK and
  France
• Full refund to payor if patient does not achieve
  50 biomarker reduction
• Oncotype DX
• 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
29
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.ht
ml?_r1orefslogin Nature Reviews, Drug
Discover December 2007, v 6, p
945 www.nice.org.uk/nicemedia/pdf/MyelomaDofHSumma
ryResponderScheme.pdf
30
Velcade For Multiple Myeloma

• 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) gt 50 reduction of serum
  M protein PAID
• Minor or Minimal response (MR) lt 50 reduction
  of serum M protein - REFUND

www.nytimes.com/2007/07/14/business/14drugprice.ht
ml?_r1orefslogin Nature Reviews, Drug
Discover December 2007, v 6, p
945 www.nice.org.uk/nicemedia/pdf/MyelomaDofHSumma
ryResponderScheme.pdf
31
Pathologist Fear? New Sample Types Beyond Tissue

• Molecular Blood Tests
• Breath Tests
• Urine Tests

32
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
33
Pathologist Fear? New Technology Beyond
Morphology

• Gene Expression Differentiates Burkitt
  Lymphoma from Diffuse Large B Cell Lymphoma,
  Improving Patient Care

Louis Staudt, MD, PhD, National Cancer Institute
34
Pathologist Fear?Molecular Tests are Exploding
Source In Development Coalition for 21st
Century Medicine Survey 2007
35
Venture Capital is focused on DX
Increased Venture Capital Spending
Nature Biotechnology Volume 24 Number 8 August
2006, BioCentury's BCIQ, Genzyme Analysis
36
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
• 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
37
Personalized Medicine- Friend or Foe?

• What is it?
• Why now?
• When will it be real?
• Call to Action

38
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
39
Call to ActionFriend 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
40
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
41
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

42
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

43
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

44
Future Health Care Spending
Individual Health Care Spending Curve
Current Practice
Improved Quality of Life Financial Savings
Health Care
Potential of Personalized Medicine
Investment In Diagnostics And Prevention
Years
Source Deloitte Development LLC 2006
45
Acknowledgements

• David Turnquist, Boston College
• Deloitte Center for Health Solutions
• Personalized Medicine Coalition

46
(No Transcript)
47
TRANSFORMING PATHOLOGYEmerging technology
driving practice innovation