Pharmacogenomics for Clinical Use and in Drug Development

Published by: TriMark Publications

Published: Jun. 1, 2009 - 244 Pages

Table of Contents

1. Overview

1.1 Statement of Report

1.2 Objectives of this Report

1.3 Scope of the Study

1.4 Methodology

1.5 Executive Summary

2. Introduction

2.1 Pharmacogenomic Testing Overview

2.1.1 Clinical Applications

2.1.2 Technologies for Pharmacogenomic Diagnostic Tools

2.1.3 Drug and Diagnostic Combinations

2.1.4 Economic Impact of Healthcare Costs

2.2 Genetic Variation among Individuals

2.2.1 Population Genomics

2.2.2 SNPs and Haplotypes

2.2.3 HapMap

2.2.3.1 The International HapMap Project

2.2.3.2 HapMap Participants and Funding Sources

2.3 Drug Metabolism

2.3.1 Adverse Drug Reactions (ADRs)

2.3.2 Drug-Test Combinations

2.4 Impact of Pharmacogenomics

2.4.1 How Will Gene Variation Be Used in Predicting Drug Response?

2.4.2 How Will Drug Development and Testing Benefit from Pharmacogenomics?

2.4.3 Advantages of Pharmacogenomics

2.4.4 The Diagnostics-Therapeutics Fusion

2.4.5 Potential Challenges

2.4.6 Poor Metabolizer Phenotype Testing

2.4.7 Drug Repositioning

2.5 Pharmacogenomic Tests

2.5.1 CYP2D6

2.5.2 CYP2C19 and CYP2C9

2.5.3 CYP3A4 and CYP3A5 Genotyping

2.5.4 CYP1A2 and CYP2B6

2.5.5 NAT2, DPD, and UGT1A1

2.6 HercepTest

2.7 Drivers of Pharmacogenomic Testing

2.8 Pharmacogenomics and Drug Discovery

2.8.1 Business Implications of Pharmacogenomics in Drug Discovery

2.8.2 Impact of Pharmacogenomics on Drug Sales

2.8.3 Pressure to Optimize Drug Discovery Drives Use of Pharmacogenomics

3. Pharmacogenomic Testing Market: Size, Growth and Share

3.1 Global Pharmacogenomic Testing Markets by Technology Segments

3.1.1 Market Structure

3.1.2 Market Drivers in the Pharmacogenomic Diagnostics Testing Sector

3.1.3 Market Restraints in Pharmacogenomic Diagnostic Testing Segment

3.1.4 Principal Market Segments for Genomics Testing

3.1.4.1 Diagnostic Testing

3.1.4.2 Pharmacogenomic Testing

3.1.4.3 SNP Identification

3.1.5 Key Players in the Pharmacogenomic Diagnostics Testing Segment

3.1.6 Pharmacogenomic Testing Sector Analysis

3.2 U.S. Pharmacogenomic Testing Market

3.2.1 Market Overview

3.2.2 Diagnostic Testing Categories

3.3 European Pharmacogenomic Diagnostic Testing Market

3.4 Japanese Diagnostic Testing Market

4. Pharmacogenomic Disease Markers

4.1 SNPs

4.1.1 SNP Identification Market

4.1.2 Overview of SNP Identification

4.1.3 Strategies for SNP Identification

4.1.4 Candidate Gene Selection

4.1.5 Whole-Genome Linkage Disequilibrium Mapping

4.1.6 SNP Databases

4.1.7 Computational Tools for SNP Identification

4.1.8 SNPbrowser, Applied Biosystems

4.1.9 Progeny Suite, Progeny Software, LLC

4.1.10 Sentrix Array Matrix, Illumina

4.1.11 Third Wave Technologies (a Hologic Company)

4.2 Predictive Pharmacogenomics

4.2.1 Cancer Testing

4.2.2 Breast Cancer

4.2.3 Melanoma

4.2.4 Colon Cancer

4.2.5 Predictive Cancer Testing Market Size

4.2.6 Prostate Cancer

4.2.7 Lung Cancer

4.2.8 Acute Myelocytic Leukemia (AML)

4.2.9 Cystic Fibrosis

4.2.10 Genetic Test for Cardiac Ion Channel Mutations (Cardiac Channelopathies)

4.2.11 Cardiac Transplants

4.2.12 Thiopurine S-methyltransferase (TPMT) Genetic Test

4.2.13 CARING Study

4.2.14 Vilazodone

4.2.15 STRENGTH Trials (Statin Response Examined by Genetic HAP Markers)

4.2.16 HIV and AIDS

4.2.17 Herceptin and Tykerb

4.2.18 Asthma

4.2.19 Hepatitis C Viral Load

4.3 Examining the Impact of Pharmacogenomics in Specific Disease Application

4.3.1 The Impact of Pharmacogenomics in Bipolar and Other Psychiatric Disorders

4.3.2 Pharmacogenomics in Warfarin Treatment

4.3.3 Pharmacogenomics and Breast Cancer Treatment

4.3.4 Pharmacogenomics of Depression

4.3.4.1 Tricyclic Antidepressants

4.3.4.2 Serotonin Re-uptake Inhibitors

4.3.4.3 Mirtazapine and Venlafaxine

4.3.4.4 Nefazodone, Moclobemide, Reboxetine and Trazodone

4.3.5 Pharmacogenomics of Cardiovascular Disease

4.3.5.1 Beta-blockers

4.3.5.2 Angiotensin II Type 1 Receptor Antagonists and AT1 Receptor Antagonists (Sartans)

4.3.6 Pharmacogenomics of Thromboembolic Disorders

4.3.6.1 Warfarin

4.3.6.2 Acenocoumarol

4.3.6.3 Phenprocoumon

4.4 Gene Chips to Detect Cytochrome Variations

4.4.1 AmpliChip CYP450—Roche Diagnostics

4.4.2 GeneChip System—Affymetrix

4.4.3 NanoChip Molecular Biology Workstation—Nanogen, Inc.

5. Pharmacogenomic Testing: Development Issues

5.1 Adoption of Pharmacogenomic Testing

5.1.1 Pharmacogenomics Gatekeepers

5.1.1.1 Industry

5.1.1.1.1 Use of Pharmacogenomics in Drug Development

5.1.1.1.2 Co-development of Pharmacogenomics Diagnostics and Drugs

5.1.1.2 FDA as a Gatekeeper of Pharmacogenomics

5.2 Factors Influencing the Integration of Pharmacogenomics into Clinical Trials

5.3 Moderators of Growth

5.3.1 Classification of Extensive vs. Poor Metabolizer

5.3.2 Genetic Testing

5.3.3 Cost-Benefit of Pharmacogenomic Testing

5.3.4 Workforce Issues

5.3.5 Reimbursement

5.3.6 New CPT Test Codes and Payment Amounts

5.3.7 CMS and Other Third-party Payers

5.3.7.1 Reimbursement Challenges to Pharmacogenomic Testing

5.3.7.2 CMS Regulatory Responsibilities

5.3.7.3 Costs Associated with Pharmacogenomic Testing

5.4 Clinical Guidelines and Pharmacogenomic Testing

5.5 Good Laboratory Practice (GLP)

5.6 Quality Assurance Issues

5.6.1 Criteria Required to Establish a Genomic Test for Clinical Use

5.6.2 Microarrays in Clinical Diagnostic Use

5.7 Pre-therapeutic Pharmacogenomic Testing

5.8 Regulatory Requirements

5.9 Screening

5.10 Cost of Phenotyping vs. Genotyping

5.11 Pharmacogenomic Tests: New Product Development

5.12 Underutilization of Pharmacogenomic Tests

6. Business Trends in the Industry

6.1 Pharmacogenomic Initiatives within Pharmaceutical Companies

6.2 Pharmacogenomic Testing Growth Factors

6.3 Acquisition, License Agreements, Internal Development and Partnerships

6.4 Product Testing Depth in Pharmacogenomic Testing

6.5 Government Regulation

6.5.1 U.S. Regulations

6.5.2 U.K. Regulations

6.5.3 E.U. Regulations

6.5.4 Japanese Regulations

6.6 Increased Market Penetration in Pharmacogenomic Testing

6.7 Legal Issues

6.7.1 Federal Policy History

6.7.2 State Policy History

6.7.3 Federal Anti-Discrimination Laws and How They Apply to Genetics

6.7.3.1 The Genetic Information Nondiscrimination Act of 2008 (GINA)

6.7.4 Prescription Drug User Fee Act (PDUFA)

6.7.5 Liability Concerns for Pharmacogenomics Drug and Diagnostic Developers

6.8 Barriers to Growth

6.9 Drivers of Growth

6.10 Product Launches and Developments

6.11 Investment Parameters for Diagnostic Companies

6.12 Key Elements of the Pharmaceutical Value Chain

6.13 An Evaluation of Successful Pharmacogenomic Business Models

6.14 Ethical Considerations for Pharmacogenomic Applications

6.15 Drug Repositioning Services

6.16 Patent Protection of Pharmacogenomic Technology

6.17 FDA Product Submission and Review Process

6.18 FDA Pipeline for Pharmacogenomic Tests

6.19 Adaptive Clinical Trial Design

7. Important Technology Trends in Pharmacogenomics

7.1 Trends in Pharmacogenomic Testing

7.1.1 Toxicogenomics

7.2 Drug Metabolism

7.3 Personalized Medicine: the Genomic and Proteomic Approach

7.4 Biomarkers

7.4.1 Cancer

7.4.1.1 Leukemia: Gleevec and Dasatinib (BMS-354825)

7.4.1.2 Gefitinib (Iressa)

7.4.1.3 Colorectal Cancer

7.5 Cardiovascular Drugs

7.5.1 Arrhythmia

7.5.2 Hypertension

7.5.3 Hyperlipidemia

7.5.4 Myocardial Infarction

7.5.5 Heart Failure

7.6 Future Developments

7.6.1 GSK’s Pharmacogenomic Program

7.6.2 Roche’s Biomarker Strategy

7.6.3 Hypertension Markets

7.6.4 Expression Data to Integrate Pharmacology and Chemistry Data

7.6.5 Metabolomics

7.6.6 Theranostics

8. Overview and Conclusions

8.1 The Unrealized Promise of Pharmacogenomics

8.2 The New Drug Pipeline

8.3 Pharmacogenomics and Regulation

8.4 Pharmacogenomics and Reimbursement

8.5 Key Considerations for Realizing the Promise of Pharmacogenomics

8.6 Development of Easy to Use Point of Care Pharmacogenomic Tests

8.7 Development of Pharmacogenomic Tests during Drug Development

8.8 Pharmacogenomics’ Impact on Commercial Strategies

8.9 Pharmacogenomics’ Impact on the Blockbuster Model of Drug Development

8.10 Pharmacogenomics’ Impact on Clinical Trials

8.11 Pharmacogenomic Business Models

8.12 Structure of Pharmacogenomic Deals and Alliances

8.13 Challenges to Pharmacogenomics

9. Company Profiles

9.1 Abbott Laboratories

9.2 Affymetrix

9.3 Agilent Technologies, Inc.

9.4 Ambry Genetics

9.5 ARCA Biopharma, Inc.

9.6 Asper Biotech

9.7 AstraZeneca

9.8 Bayer

9.9 BioTrove, Inc.

9.10 Bristol-Myers Squibb

9.11 Celera Group

9.12 Clinical Data

9.13 CombinatoRx, Inc.

9.14 Complement Genomics Ltd.

9.15 Covance Inc.

9.16 CuraGen Corporation

9.17 Cypress Bioscience, Inc.

9.18 Dako (formerly DakoCytomation)

9.19 deCODE Genetics

9.20 DNAPrint Genomics

9.21 DxS

9.22 EraGen Biosciences

9.23 EXACT Sciences

9.24 Expression Analysis

9.25 FivePrime Therapeutics

9.26 GE Healthcare

9.27 Gene Express, Inc.

9.28 GeneGO Inc.

9.29 Genelex Corporation

9.30 Genentech

9.31 Genizon Biosciences Inc.

9.32 Genomic Health

9.33 Gentris

9.34 Genzyme

9.35 GlaxoSmithKline

9.36 g-Nostics Ltd.

9.37 Hologic

9.38 Human Genome Sciences

9.39 Illumina

9.40 Incyte, Inc.

9.41 InterGenetics Inc.

9.42 Interleukin Genetics

9.43 Iris BioTechnologies Inc.

9.44 Johnson & Johnson

9.45 Lab21

9.46 Life Technologies Corporation

9.47 Luminex Corp.

9.48 MediBIC Group

9.49 Melior Discovery Inc.

9.50 Merck & Co.

9.51 Merck Serano

9.52 Millennium Pharmaceuticals

9.53 Monogram Biosciences, Inc.

9.54 Myriad Genetics, Inc.

9.55 Nanogen

9.56 Nanosphere

9.57 Nitromed

9.58 Ocimum Biosolutions

9.59 Orchid Cellmark

9.60 Ore Pharmaceuticals

9.61 PharmaSeq

9.62 Prediction Sciences

9.63 Predictive Biosciences

9.64 Prometheus Laboratories

9.65 Progeny Software, LLC

9.66 Roche Diagnostics

9.67 Response Genetics, Inc.

9.68 Sequenom

9.69 SimuGen Ltd.

9.70 Sosei Group Corporation

9.71 Transgenomic, Inc.

9.72 TrimGen Corp.

9.73 Tripos International

9.74 Vertex Pharmaceuticals

9.75 VIA Pharmaceuticals, Inc.

9.76 Warnex

9.77 Wyeth

9.78 XDx, Inc.

INDEX OF FIGURES

Figure 2.1: Roche AmpliChip

Figure 2.2: FDA Approval Rates for NME Drug Applications vs. R&D Expenditures, 1998-2008

Figure 2.3: Steps Involved in Bringing a Drug to Market

Figure 2.4: CYP2C9

Figure 6.1: Total Spending on Healthcare in the U.S., 1960-2008

Figure 6.2: The Healthcare Dollar, 2008

INDEX OF TABLES

Table 1.1: The Success of Pharmacogenomics: Drugs that Utilize Companion Tests, 2008

Table 2.1: The Difference between Pharmacogenomics and Pharmacogenetics

Table 2.2: Clinical Applications of Diagnostic Pharmacogenomic Testing

Table 2.3: Comparison of New Molecular Entity Outcomes for FDA and EMEA (Jan 2006 - October 2008)

Table 2.4: Timeline for Development of Companion Diagnostics

Table 2.5: Valid Genomic Biomarkers in the Context of FDA-Approved Drug Labels

Table 2.6: Potential Benefits of Biomarkers as Companion Diagnostics in Drug Development

Table 2.7: Groups Participating in the International HapMap Project

Table 2.8: High-Profile Drug Withdrawals from the Marketplace

Table 2.9: Response Rates of Patients to a Major Drug for Selected Therapeutic Areas

Table 2.10 Factors That Determine a Successful Pharmacogenomic Test

Table 2.11: Pharmacogenomics’ Influence on Drug Sales

Table 2.12: Pharmacogenomics’ Effect on Maximizing R&D Productivity

Table 2.13: Prevalence of Metabolically-Active Enzymes

Table 2.14: Pharmacogenomics in Phase II and Phase III Trials

Table 2.15: Drug Testing

Table 2.16: Factors Affecting Variability in Individual Response to Drug Therapy

Table 2.17: CYP2D6 Characteristics

Table 2.18: CYP2D6 Metabolism of Drug Types

Table 2.19: CYP2C19

Table 2.20: CYP2C19 Metabolism of Drug Types

Table 2.21: CYP2C9 Characteristics

Table 2.22: CYP2C9 Metabolism of Drug Types

Table 2.23: CYP3A4/5/7 Metabolism of Drug Types

Table 2.24: CYP1A2 Metabolism of Drug Types

Table 2.25: CYP2B6 Metabolism of Drug Types

Table 2.26: Drivers of Pharmacogenomic Testing

Table 2.27: Markets for Pharmacogenomic Testing

Table 3.1: Worldwide Pharmacogenomic Market Size by Technology Segments,2004-2012

Table 3.2: Total Pharmacogenomic Testing Market Size, 2001-2012

Table 3.3: Diagnostic Pharmacogenomic Testing Market Size, 2001-2012

Table 3.4: Benefits of Pharmacogenomic Diagnostics in Patient Care

Table 3.5: Genotyping Pharmacogenomic Testing Market Size, 2001-2012

Table 3.6: Benefits of Pharmacogenomics in Clinical Trials and Drug Development

Table 3.7: Five Key Action Points for Pharmaceutical Companies

Table 3.8: Global SNP Identification Tools Market Size, 2004-2012

Table 3.9: Pharmacogenomic Testing Market Structure

Table 3.10: P450 Isozymes and Pharmaceuticals

Table 3.11: List of Companies that Market Pharmacogenomic Tests

Table 3.12: Key Collaborations in the Pharmacogenomics Industry

Table 3.13: Prominent Drugs Withdrawn from the Market

Table 3.14: Key Elements in the Drug Development Process

Table 3.15: Major Suppliers of PCR-based Assays and PCR-based Technologies

Table 4.1: Methods for Performing NAT

Table 4.2: SNP Databases

Table 4.3: Myriad Genetics Predictive Medicine Sales, 2001-2008

Table 4.4: DNA-based Predictive Medicine Product Sales for Cancer, 2006-2010

Table 4.5: Developmental Atherosclerosis Drugs

Table 4.6: Summary of Assays for HIV Viral Load Testing

Table 4.7: U.S. Market Share of HIV Testing Kits

Table 4.8: Global HIV Statistics, 2007

Table 4.9: List of Approved HIV/AIDS Rapid Test Kits, 2009

Table 4.10: Monogram Bioscience, Inc. Products for HIV Testing

Table 4.11: CCR-5 Receptor Agonists in Development, 2009

Table 4.12: Asthma Therapeutic Drug Pipeline

Table 4.13: Psychiatric Case Studies, Organized Pharmacokinetically

Table 4.14: Antidepressant Drugs Decreased Clearance with DME CYP2D6

Table 4.15: Antidepressant Drugs with No Effect Clearance with DME CYP2D6

Table 5.1: Examples of Gene-Drug Pharmacogenomic Relationships

Table 5.2: Estimated Cost and Time for Typing of the BRCA1 Gene by Direct Sequencing vs. SNP Array

Table 5.3: Average Cost of Resistance Testing, 2007

Table 6.1: U.S. Prescription Drug Expenditures, 2003-2015

Table 6.2: U.S. Pharmaceutical Market, 1996-2009

Table 6.3: Top Ten Global Pharmaceutical Companies by Global Sales, 2007

Table 6.4: Pharmaceutical Companies Ranked by Total R&D Expenditures, 2007

Table 6.5: Leading Therapy Classes for R&D, 2008

Table 6.6: Leading Therapy Classes by Global Pharmaceutical Sales (Audited Market), 2007

Table 6.7: Number of NME Approvals and Mean Approval Times, 1984-2008

Table 6.8: Global Market for Tools and Consumables Used in Drug Discovery and

Development, 1999-2010

Table 6.9: Leading Therapeutic Classes by U.S. Sales, 2006 and 2007

Table 6.10: Top Ten Therapeutic Classes by U.S. Dispensed Prescriptions, 2006 and 2007

Table 6.11: Top Ten Brand Drugs by U.S. Retail, 2007

Table 7.1: Select Companies Developing Cancer Diagnostics Available as Analyte Specific Reagents (ASRS)

Table 7.2: Emerging Fields in Biological Science with the Potential to Impact Personalized Medicine

Abstract

About MarketResearch.com
MarketResearch.com is an online aggregator selling over 250,000 market research reports, company profiles and country profiles from over 650 research firms. Our reports will provide you with the critical business and competitive intelligence you need for strategic planning and marketing research. Coverage includes the US, UK, Europe, Asia and global markets.