治療薬・診断薬の合剤：R&D動向および商業的成功因子

Abstract

This new report from CHI' s Insight Pharma Reports assesses the commercial opportunities and provides the information and guidance that companies need to steer clear of the pitfalls in combination drug/diagnostic R&D. Specifically, it provides:

• A quantitative survey, rendered in easy-to-scan charts, of the industry' s views, plans, and current actions with regard to combination drug/diagnostic products
• A review of drug/diagnostic combinations in current use such as Monogram Bioscience' s Trofile Assay, which was co-developed with Pfizer' s Celsentri (for HIV) as a means to identify responders to the drug
• A review of existing safety and status biomarkers that are being used as diagnostics, such as a simple genotyping test to guide warfarin dosing, or molecular markers for identifying responders to Gleevec and Nexavar
• Patenting activity around combination drug/diagnostic products in cancer, neurodegenerative disease, respiratory disease, and viral infection
• The current state and outlook for reimbursement of diagnostics, including a case study of Genomic Health' s Oncotype DX gene expression test for predicting the benefits of chemotherapy in newly diagnosed breast cancer patients
• A model of the potential expansion of a therapeutic market generated by incremental improvements in biomarker test sensitivity
• Implications of FDA' s IVDMIA and ASR draft guidances

As innovative technology drives down the cost of biomarker discovery, and knowledge accumulates about the multigenic, multi-target nature of complex diseases such as cancer, the demand will surge for diagnostics that can detect the molecular variation underlying disease, and facilitate the prescription of the right drug. Participants in CHI' s survey (individuals involved with the planning and development of combination drug/diagnostic products) revealed fattening pipelines and the firm conviction that the drug and the diagnostic must be developed concurrently and "arrive together". Respondents overwhelmingly held the view that reimbursement and clear regulatory pathways will be the most significant determinants of the future viability of drug/diagnostic pairs.

The trends are aligning to favor the development and commercialization of drug/diagnostic pairs:

• Growth in the molecular diagnostic market in terms of unit volume, sales, and venture capital investment
• Lower costs to discover biomarkers
• Easing regulations governing Medicare reimbursement of molecular tests
• Compelling market precedents that patient stratification through combination drug and diagnostic is commercially rewarding

Combination Drug/Diagnostic Products: Pathways to R&D and Commercial Success is a rigorous evaluation of the therapeutic and commercial potential of combinations that are either co-developed, already in use for approved drugs, or in development to approve the focus and efficacy of existing drugs.

Table of Contents

CHAPTER 1 THE BURNING PLATFORM: COSTS, COMPLICATIONS, COMPLIANCE

• 1.1. Drug Development Expenses Are Increasing at an Alarming Rate
• 1.2. Postlaunch Adverse Reactions Are Increasing
• 1.3. Strategies for Streamlining Drug Development and Use
  • Individualized Drug Dosing
  • Monitoring Patient Response to a Drug or Drug Candidate

CHAPTER 2 BIOMARKERS: AXIS OF INNOVATION FOR DIAGNOSTICS AND THERAPEUTICS

• 2.1. Limitations of Protein Biomarker Discovery in Blood
• 2.2. Examples of Drug/Diagnostic Combinations Currently in Use
  • Genomic Health: Oncotype DX
  • Clinical Data: Phase III Tandem of Vilazodone and Marker
  • Roche: C-Reactive Protein as a Response Biomarker with Antibody Therapy
  • Oncogene Science: HER2/neu Testing with Herceptin and Vascular Endothelial Growth Factor and KDR Testing with Nexavar
  • Sidebar: Monogram Biosciences' Trofile Assay: Co-developed for Use with Pfizer' s Celsentri for HIV
  • Celera Genomics: Cirrhosis in Chronic Hepatitis C Patients
• 2.3. Existing Biomarkers Used as Diagnostics
  • Apolipoprotein E Genetic Variants and Alzheimer' s Disease
  • Imatinib (Gleevec): A Genomically Targeted Therapy
  • Thiopurine Methyltransferase
  • Irinotecan (Camptosar)
  • Warfarin

CHAPTER 3 DIAGNOSTIC TOOLS TO IMPROVE DRUG DISCOVERY AND THE PRESCRIPTION OF LICENSED DRUGS

• 3.1. Discovering New Drugs that Work Well in the Entire Population
• 3.2. Discovering New Targeted Drugs Aimed at Genomic Subpopulations
• 3.3. Approaches to Improve the Safety and Efficacy of Drug Development
  • "Rescue" of Products in Late-Stage Trials Due to Adverse Drug Reactions
  • Creation of New Drugs for Particular Subpopulations of "Good Responders"
• 3.4. Improving the Prescription of Licensed Drugs
  • Preprescription Screening to Identify Patients at Risk for Adverse Drug Reactions
  • Postmarketing Surveillance of Approved Drugs
  • Preprescription Screening to Identify Good Responders
  • Use of Efficacy Data in Drug Marketing

CHAPTER 4 THE LABORATORY: CLINICAL DIAGNOSTICS DELIVERY MODEL

• 4.1. Quality Assurance and Validation Requirements of Pharmacogenomic Testing
• 4.2. National Academy of Clinical Biochemistry Guidelines and Recommendations
• 4.3. Metabolism Gene Variants as Markers for Therapeutic Response
  • Cytochrome P450 System
  • CYP2D6
  • CYP2C9
  • CYP2C19

CHAPTER 5 APPLYING DIAGNOSTICS TO HEALTH CARE AND THERAPEUTIC DEVELOPMENT

• 5.1. Open Databases as a Platform for Diagnostics/Therapeutics Co-development
• 5.2. Test Validation Is Key
• 5.3. Opportunities for Future Pharmacogenetic/Drug Companion Tests: 3 Examples
  • Abacavir (Ziagen)
  • Amoxetine (Strattera)
  • Proton Pump Inhibitors

CHAPTER 6 ASSESSING THE MARKET POTENTIAL FOR COMBINATION PRODUCTS: PATHWAYS TO SUCCESS

• 6.1. CHI Insight Pharma' s Proprietary Survey Results
  • Characteristics that Recommend a Drug for Combination Rx/Dx Development
  • Disease States Best Suited for Combination Rx/Dx Development
• 6.2. Market Dynamics
  • The Molecular Diagnostics Segment Shows Robust Growth
  • A Diagnostic Market Characterized by Consolidation
  • The US Diagnostic Market: Historically Low Expectations
• 6.3. Trends in Drug/Diagnostic Development Point to Growth
  • The Industry Sees Broad Opportunities for Combination Rx/Dx Development
  • Projected Growth in the Rx/Dx Pipeline
• 6.4. Big Pharma' s Reluctance to Abandon the Blockbuster Model
• 6.5. Industry Views on Where and When Combination Strategies Will Be Deployed
  • Commentary from Industry Leaders, by Sector
  • Players Poised to Succeed in the Brave New World of Targeted Therapies and Companion Diagnostics
• 6.6. Pathways to Successful Development of Combination Drug/Diagnostic Products
  • Momentum Toward the Concept of Parallel Development of the Drug and the Diagnostic
  • Momentum Toward a Developmental Focus on Both the Disease and the Therapy
• 6.7. Reimbursement and Regulatory Incentives Will Drive Adoption
  • Diagnostic Coding Requirements: An Outdated Hurdle to Adoption?
  • A Case Study in Reimbursement for a Molecular Diagnostic: Genomic Health' s Oncotype DX
• 6.8. Understanding Specific Disease-Related Diagnostic Opportunities in the Cancer Space
• 6.9. Sectors and Strategies that Will Drive Combination Drug/Diagnostic Development
  • What Types of Companies Will Pursue a Combination Model?
  • What Execution Strategy Will Most Companies Pursue?

CHAPTER 7 INTELLECTUAL PROPERTY PROTECTION

• 7.1. Where We' ve Been
• 7.2. Where We' re Going
• 7.3. Implications for Technological Protection and Remuneration
• 7.4. Strategies in Play
  • Therapy-Centric
  • Genetic/Proteomic Discovery
  • Diagnostic-Centric
• 7.5. A Snapshot of Drug/Diagnostic Patent Applications Filed in the Second Quarter of 2005
  • Cancer
  • Respiratory Diseases
  • Neurodegenerative Diseases
  • Viral Infections

CHAPTER 8 REGULATORY CONSIDERATIONS: RECENT FDA REGULATIONS AND GUIDANCES

• 8.1. The Regulation of Combination Products
• 8.2. FDA' s Office of Combination Products (OCP)
• 8.3. The OCP' s Charter: GMP Requirements and Adverse Event Reporting
• 8.4. FDA Endorses Retrospective Studies
• 8.5. Real-Time Review
• 8.6. Relevant and Recent Regulatory Actions Bearing on Combination Drug/Diagnostics
  • 510(k) or Full Premarket Approval (PMA)?
  • Draft Guidance for Industry, Clinical Laboratories, and FDA Staff; In Vitro Diagnostic Multivariate Index Assays (FDA; September 2006)
  • Summary
  • Draft Guidance for Industry and FDA Staff, Commercially Distributed Analyte- Specific Reagents (ASRs): Frequently Asked Questions (FDA; September 2006)
  • Essential Regulatory Elements
  • Definition of an ASR: The Key Delineation
  • The Advanced Laboratory Diagnostics Act of 2006 (House of Representatives; May 2006)
  • Drug-Diagnostic Co-development Concept Paper (FDA; April 2005)
  • Memorandum of Understanding between the FDA, NCI, and CMS (FDA, NCI, CMS; January 2006)

CHAPTER 9 THE FUTURE IS NOW: CLINICAL TRIAL UPDATE

• 9.1. MINDACT
  • Trial Summary
• 9.2. TAILORx
  • Trial Summary

References

Glossary of Selected Terms

Company Index with Web Addresses