Author: Lucy Jean Sannes, Ph.D., M.B.A.
EXECUTIVE SUMMARY
CHAPTER 1
INTRODUCTION
CHAPTER 2
OVERVIEW OF PERSONALIZED MEDICINE
2.1 What is Personalized Medicine? What are Drug/Diagnostic Combinations?
Drug/Diagnostic Combinations
2.2 Selected Terms Used in Personalized Medicine
Pharmacogenomics
Pharmacogenetics
Other Terms Used in Personalized Medicine
2.3 Disease Applications in Personalized Medicine
2.4 Diagnostic Technologies Used in Personalized Medicine
CHAPTER 3
SELECTED EXAMPLES OF PERSONALIZED MEDICINE AVAILABLE TODAY
3.1 Cytochrome P450 and Drug Metabolism
CYP2D6 Phenotype and Response to Tamoxifen
Cytochrome P450 Enzymes and Other Drugs
3.2 Estrogen Receptor and Progesterone Receptor Status and Hormone Therapy for Breast Cancer
3.3 HER2 Overexpression and both Herceptin and Tykerb - Tests for HER2 Overexpression Alone and in Combination with Other Biomarkers
3.4 Multi-Gene/Biomarker Tests for Determining Breast Cancer Prognosis and Treatment
Agendia‘s MammaPrint
Applied Genomics’ MammoStrat
bioTheranostics’ Theros Breast Cancer Index
Genomic Health’s Oncotype DX
Ipsogen’s MapQuant Dx Genomic Grade
3.5 Multi-Gene/Biomarker Tests for Determining Diagnosis, Prognosis and Treatment of Other Cancers
Applied Genomics‘ PulmoType
Aureon Laboratories’ Prostate Px
bioTheranostics’ Theros CancerTYPE ID
Pathwork Diagnostics’ Pathwork Tissue of Origin Test
3.6 Epidermal Growth Factor Receptor (EGFR)
Currently Available Therapies That Target EGFR
Testing for Expression of EGFR
Testing for EGFR Mutations
DxS (now part of Qiagen)
Genzyme Genetics
AutoGenomics
3.7 KRAS Mutations and Anti-EGFR Therapy for Colorectal Cancer
3.8 BRAF Mutations and Anti-EGFR Therapy for Colorectal Cancer
3.9 UGT1A1 Genetic Variants and Treatment with Camptosar (irinotecan)
Hologic
AutoGenomics
3.10 DPYD and TYMS Variants and 5-Flurouracil Therapy
Myriad Genetics
AutoGenomics
Others
3.11 Biomarkers in Leukemia and Lymphoma
Gleevec and Other Tyrosine Kinase Inhibitors for Treatment of Philadelphia Chromosome Positive CML
Philadelphia Chromosome and Busulfan
PML/RAR and Vesanoid (tretinoin)
Rituxan and Other Antibodies That Target CD20 Antigen for Treatment of Lymphoma or Leukemia
Many Additional Biomarkers for Leukemia and Lymphoma
3.12 Personalized Medicine and HIV Therapy - Moving Beyond HIV Viral Load and Drug Resistance Testing
HLA-B*5701 Testing and Hypersensitivity to Abacavir
CCR5-Tropic HIV and Selzentry (maraviroc)
3.13 CYP2C9 and VKORC1 Variants and Warfarin Dosing
3.14 Thiopurine Methyltransferase and Metabolism of Thiopurine Drugs
3.15 Selected CNS Applications of Personalized Medicine
HLA-B*1502 and Carbamazepine
PGxPredict:CLOZAPINE
3.16 Selected Other Personalized Medicine Tests
CHAPTER 4
DEVELOPMENT OF DRUG/DIAGNOSTIC COMBINATIONS - PERSONALIZED MEDICINE PRODUCTS
4.1 Identification of Personalized Medicine Biomarkers
4.2 Validation of Diagnostic Tests for Personalized Medicine
4.3 Development and Regulatory Issues Facing Diagnostic Companies in Personalized Medicine
Regulatory Issues and Consideration for Clinical Laboratories with Laboratory Developed Tests for Personalized Medicine
Regulatory Issues and Consideration for Diagnostics Companies in Personalized Medicine
The two basic review processes
4.4 Development and Regulatory Issues Facing Therapeutic Companies in Personalized Medicine
4.5 Selected Personalized Medicine Examples - What Tests are Used by Physicians?
Why Isn’t Warfarin Sensitivity Testing Performed Routinely Now?
Screening for HLA-B*5701 Hypersensitivity to Abacavir
Genomic Health and Validation of OncoType DX
Agendia and Validation of MammaPrint
CHAPTER 5
STRATEGIC ISSUES FACING PHARMACEUTICAL AND DIAGNOSTIC COMPANIES DEVELOPING PERSONALIZED MEDICINE PRODUCTS
5.1 Need for More Research and Understanding
Biomarkers and Other Factors Influencing Response to Therapy
Validation Studies and Outcome Studies
Other Research and Information Needs
5.2 Models/Options for Pharmaceutical Companies Developing Drug/Diagnostic Combinations
5.3 Models/Options for Diagnostic Companies Developing Personalized Medicine Tests - Test Development
5.4 Delivery of New Diagnostic Tests - IVD versus CLIA Laboratory
5.5 Health Economics, Reimbursement, and the Payers’ Perspective
Health Economic Studies for Personalized Medicine Tests
Perspectives Expressed in Expert Interviews
Payer Perspectives and Policies
Medco Health Solutions
Generation Health
5.6 Intellectual Property Issues
5.7 Penetrating the Market
Does the Test Affect Physicians’ Decisions?
Acceptance by Experts; Incorporation into Guidelines
Physician Education
CHAPTER 6
COMPANY PERSPECTIVES ON PERSONALIZED MEDICINE
6.1 Potential Benefits, Risks, and Challenges for Biopharmaceutical and Pharmaceutical Companies
6.2 Potential Benefits, Risks, and Challenges for Diagnostic Companies
CHAPTER 7
POTENTIAL OPPORTUNITIES FOR THE FUTURE
7.1 Tests in Development for Prediction of Breast Cancer Prognosis and Determining Treatment
Agendia
Applied Genomics (Subsidiary of Clarient)
Celera
Genomic Health
Nuvera Biosciences
Prediction Sciences and Clarient
Additional Tests in Development for Prediction of Breast Cancer Prognosis and Determining Treatment
7.2 Tests in Development for Determining Prognosis and Treatment of Other Cancers
Agendia
Applied Genomics (Subsidiary of Clarient)
Genomic Health
Additional Tests in Development for Prediction of Prognosis and Determining Treatment for Other (Non-Breast) Cancers
7.3 Other (Non-Cancer) Personalized Medicine Tests in Development and/or Used in Pharmaceutical Research
7.4 Pharmaceutical/Diagnostic Company Agreements
CHAPTER 8
EXPERT INTERVIEWS
Howard C. Coleman, Chief Executive Officer, Genelex Corporation
Cornelius Diamond, CEO, Prediction Sciences
Richard Ding, Chief Executive Officer and bioTheranostics (A bioMerieux Company) & Vice President of Strategy and Business Development at bioMerieux (the parent company)
Stephen Eck, M.D., Ph.D., Vice President, Translational Medicine & Pharmacogenomics, Eli Lilly
Paul Harkin, President & Managing Director, Almac Diagnostics
Fareed Kureshym, Founder, Chairman, President and CEO, AutoGenomics
Stephen Little, Vice President of Personalized Medicine, Qiagen, Former CEO and Founder of DxS (which was acquired by Qiagen)
REFERENCES
COMPANY INDEX WITH WEB ADDRESSES