薬物診断の技術、競争と市場モデル

Pharmacodiagnostics: Technologies, Competition, and Market Models examines the reasons why the business environment of pharmaceuticals is changing in favor of pharmacodiagnostics, and describes market models that are likely to emerge as the pharmaceutical and diagnostic industries collaborate to bring personalized medicine to fruition.

Personalized medicine promises safe drugs that work. By using diagnostic tests to identify, in advance of drug treatment, patients who are likely to be good responders and/or who are unlikely to suffer an adverse drug reaction (ADR), it is possible to improve the efficacy and safety of existing and new medicines. The tests themselves are referred to as pharmacodiagnostics, and their application to enable personalized medicine is poised to have a dramatic impact on the pharmaceutical industry, the diagnostic industry, and the overall provision of healthcare.

Pharmacodiagnostics and personalized medicine promise to address the key problems faced by the pharmaceutical industry. In addition to the clinical problems caused by ADRs, there are also well-documented commercial problems for the pharmaceutical industry, which has experienced a number of recent high-profile drug withdrawals due to unacceptable safety profiles. With the number of recalls increasing, the need for a solution is becoming critical. Furthermore, with the era of blockbuster drugs in decline, pharmaceutical companies need to incorporate personalized medicine into their drug sales models to decrease drug development costs, reduce the drug development cycle, and possibly resuscitate failed drugs.

The potential to develop personalized medicine is much greater now than at any time in the history of the drug industry. The raw data are available, and there are few technical hurdles to be overcome to allow the discovery and development of pharmacodiagnostic tests. However, the success or failure of pharmacodiagnostics will depend largely on the pull from the consumer for personalized medicine, or the push from industry. Indeed, a variety of market forces?regulatory, payer, provider, and consumer?will influence the acceptance of pharmacodiagnostics. Pharmacodiagnostics: Technologies, Competition, and Market Models analyzes these factors in detail.

Ultimately, the rise of pharmacodiagnostics will necessitate collaborative relationships between pharmaceutical and diagnostic companies with shifting power balances and opportunities for economies of scale and scope. The report projects that four principal relationships?Turnaround, Make-to-Order, Use-to-Order, and Integrated?are likely to exist. Each model is presented in terms of its varying degrees of financial benefit in return for investment in the development of companion products, underpinned by high-quality relationship management.

Executive Summary

Chapter 1. Introduction and Background

1.1. What Is Personalized Medicine?

1.2. Historical Perspective

Archibald Garrod and Inborn Errors of Metabolism

1.3. Differential Drug Response is Both a Clinical and a Commercial Problem

Drug Safety as a Clinical Problem

Drug Safety as a Commercial Problem

Drug Efficacy as a Clinical Problem

Drug Efficacy as a Commercial Problem

1.4. Why People Vary in Their Responses to Drugs

1.5. Personalized Medicine for Safe and Effective Therapies

1.6. Personalized Medicine - Why Now?

1.7. Impact of the Genome Sequence and Other Data on the Pharmaceutical and Diagnostic Industries - More Targets

Drug Targets - The Druggable Genome

Diagnostic Targets-The Assayable Genome

1.8. Pharmacogenetics and Other Pharmacodiagnostic Markers

1.9. Sources of Clinical Information

The Challenge of Validating Pharmacodiagnostics in Clinical Trials

Possible Scenarios for Validating Pharmacodiagnostics

1.10. What Are the Drivers of Personalized Medicine?

Pharmaceutical Industry Perspective

-Regulatory Pressure

-Competitive Pressure

-Intellectual Property

-Clinical Practice

-Consumer Demand

-Litigation

Diagnostic Industry Perspective

Consumer Perspective

-Providers

-Patients

-Physicians

Chapter 2. Technology Requirements for Pharmacodiagnostics

2.1. Technologies for Discovery, Development, and Delivery

Discovery

Pharmacodiagnostic and Drug Discovery and Development Timelines

Clinical Development

Diagnostic Delivery

2.2. Discovery Technologies

DNA - Review of Types of Genetic Variation

-SNPs

-Haplotypes - The HapMap

-Chromosomal Changes

DNA Discovery: Candidate Gene Analysis

-Hybridization

-Incorporation

-Extension

-Ligation

-Conformation

-Single-SNP Versus Multiplex Assays

Discovery Technology - Gene Scanning

-Automation-Based Methods

-Multiplex-Based Methods

-Single-Molecule Analysis

Discovery Technology - RNA

Discovery Technology - Proteins

Discovery Technology - Metabolomics

Bioinformatics

2.3. Technologies for Development: Introduction

Development Technology - DNA

Development Technology - RNA

Development Technologies - Proteins

Development Technologies - Metabolites

2.4. Technologies for Diagnostics: Introduction

Diagnostic Products and Diagnostic Services

DNA -Based Diagnostics

-Roche s AmpliChip P450 Assay

RNA-Based Diagnostics

Protein and Metabolite Diagnostics

Chapter 3. Pharmacodiagnostic Products on the Market and in Development

3.1. Introduction

3.2. Companion Products on the Market by Disease Area

Cardiovascular Disease

Infectious Disease

Oncology

-Gleevec

-Herceptin

3.3. Marketed Products Whose Strategy "By-Passed" Companion Tests

Iressa

Lovenox

3.4. Companion Products in Development

Cardiovascular Disease

-LpPLA2

Infectious Disease

-Bacterial Sepsis

-Antibiotic-Resistant Infections

-Influenza

Inflammatory Disease

-Rheumatoid Arthritis

Multiplexing

-Oncology

-Liver Disease

-Alzheimer s Disease

3.5. What About Real Partnerships?

Chapter 4. The Business Environment for Pharmacodiagnostics

4.1. Introduction

4.2. Stakeholder Issues

Pharmaceutical Industry

Diagnostics Industry

Regulators

-The United States

-Europe

-Japan

Providers

Insurers/Payers

4.3. Drivers and Barriers

External Drivers

-Regulators

-Payers

-Government

-Healthcare Providers

-Patients

Internal Drivers

-Pipelines and Processes

-Compound Attrition

-Blockbusters

-Resources, Capabilities, and Competencies

-Competition, Patents, and Generics

4.4. The Value-Adding Role of Diagnostics in Pharmaceutical Research, Development, and Marketing

4.5. The Impact on Drug Development

Reducing Cycle Times

Reducing Study Sizes

Facilitating Earlier and Better Decisions

Facilitating Regulatory Approval

4.6. The Impact on Market Uptake

Increasing Prescribing (by PCPs)

Increased Market Share

Faster Penetration of Market

Market Enlargement

Exclusivity and Defense Against Generics

4.7. Conclusions: Product Revenue Scenarios With and Without a Companion Diagnostic

Chapter 5. Market Models for Pharmacodiagnostics

5.1. Introduction

The Role of Intellectual Property

-Diagnostic Rights

-Pharmacodiagnostic Rights

-Therapeutic Targets from Biomarker Discovery

5.2. The Importance of Relationship Management

Co-Opetition

The Intermediate Organization

5.3. Target Test Profiles and Target Product Profiles

The Target Profile: Price, Position, Promotion, Place

5.4. Market Models

Methodology and Assumptions

Model 1: Turnaround

-Diagnostic Partner Power

-Revenue Mechanism

Model 2: Use to Order

-Diagnostic Partner Power

-Revenue Mechanism

Model 3: Make to Order

-Diagnostic Partner Power

-Revenue Mechanism

Model 4: Integrated Model

-The Timing Issue: Three Approaches

-Diagnostic Partner Power

-Revenue Mechanism

5.5. The Integrated Company

5.6. Conclusions

Chapter 6. Expert Interviews

David Atkins, Ph.D., Veridex LLC

Dr. Walter P. Carney, Oncogene Science (part of Bayer HealthCare)

Richard Frank, GE Healthcare

Dr. Steven I. Gutman, United States Department of Health & Human Services, FDA

Dr. Jorge Leon, Leomics Associates, Inc.

Allen D. Roses, M.D., GlaxoSmithKline

Chapter 7. Outlook

7.1. In Discovery

7.2. In Development

7.3. In Diagnostics

Appendix

References

Index