Combination Drug/Diagnostic Products: Pathways to R&D and Commercial Success

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