Companion Diagnostics: Technologies and Markets. Robert Hunter. March Report Code: BIO077C

Transcription

1 Companion Diagnostics: Technologies and Markets March 2017 Robert Hunter Report Code: BIO077C

2 Table of Contents Chapter 1: Introduction... 1 Study Goals and Objectives... 1 Reasons for Doing the Study... 1 Scope of Report... 1 Intended Audience... 2 Methodology... 2 Information Sources... 2 Analyst's Credentials... 4 Related BCC Research Reports... 4 Chapter 2: Summary and Highlights... 6 Chapter 3: Personalized Medicine Overview Overview Precision Medicine Initiative Oncology as Major Driver Potential for Personalized Medicine Biomarkers Companion Diagnostics Overview General Application Categories FDA Definition Complementary Dx FDA Cleared (510k) and Approved (PMA) Market FDA Full CDx Designation Beyond FDA Designated CDx LDTs Pharmaceutical-Diagnostic Deals Company Types In Vitro Diagnostics Companies Molecular Diagnostics Industry Companion Diagnostics Companies Laboratory Test Services Companies Biomarker Research Companies Medical Centers History of Companion Diagnostics Regulatory Aspects Key Companies Cancer Market Segment Technologies Overview Reimbursement Drivers of Adoption Barriers to Adoption Cost of CDx Development CDx Regulatory Issues FDA Route Laboratory-Developed Tests Route Choosing A Regulatory Pathway... 37

3 Obstacles Chapter 4: CDx Applications Other Than Cancer Scope Established Clinical Applications Overview Background on Clinical Genomics Early Focus on Rare Diseases Challenge of Rare Disease Clinical Trials Cystic Fibrosis Experience Driver for Laboratory-Developed Tests Newborn Screening Panel Data Aggregation and Management Patient Bias vs Asymptomatic Screening Cystic Fibrosis CTFR Diagnostics Next-Generation Sequencing Leadership Pharmacogenomics Pharmacogenomics Adoption Current Successes in Pharmacogenomics Warfarin Simvastatin Cancer Drugs Liver Enzyme CYP2C19 and CYP2D Clopidigrel Codeine Human Leukocyte Antigen B Carbamazepine Azathioprine Mental Health Antidepressants Serotonin Catechol-O-Methyltransferase Pharmacokinetic and Pharmacodynamic Genes Challenges and Future Directions Validation Infectious Disease CDx HIV Statistics and Healthcare Cost HIV Drug Market Representative Drug Companies ViiV Healthcare HIV Drug-Resistance Tests Tropism for HIV Assay Competitors of Trofile Assay Hypersensitivity Test HLA-B Applications in Vaccine Development Partnerships and Collaborations for Companion Diagnostics for Infectious Diseases Other Applications Beyond HIV Hepatitis C Genetic Test for IL28B Market Forecast... 62

4 Chapter 5: FDA Designated CDx Cancer Overview Overview of Cancer Background: Docetaxel Chemotherapy Breast Cancer Overview HER2-positive Breast Cancer Herceptin (Trastuzumab): Roche (Genentech) HercepTest (Dako Now Part of Agilent) Kadcyla: Roche (Genentech) Perjeta: Roche (Genentech) CDx for Herceptin Manufacturers of HER2 Assays Dako Corp IHC Antibody FISH, PathVysion (Abbott Laboratories) Life Technologies (Thermo Fisher) Others Other HER2 Drugs: Tykerb (Lapatinib), Novartis HER2 for Other Cancers Unmet Needs Epidermal Growth Factor Receptor Non-Small-Cell Lung Cancer Erbitux for Non-Small-Cell Lung Cancer Tarceva (Erlotinib): Roche/Astellas Iressa (Gefitinib): AstraZeneca Gilotrif (Afatinib): Boehringer Ingelheim T790M Mutation Resistance Tagrisso (Osimertinib or AZD9291, AstraZeneca) Cobas EGFR Mutation Test v2: Roche Other Drugs for Lung Cancer CDx: Therascreen (PCR) Colorectal Cancer Background: Avastin: Roche (Genentech) CDx: IHC and FISH Vectibix (Panitumumab): Amgen CDx: EGFR PharmDx Kit (Dako) Erbitux (Cetuximab): Eli Lilly (ImClone) Excluding KRAS Mutations Head and Neck Cancers EGFR CDx: Leaders and Followers Differences in the U.S. and EU KRAS Market KRAS Leaders Anaplastic Lymphoma Receptor Tyrosine Kinase Xalkori (Crizotinib), Pfizer s Approved NSCLC Therapy CDx: Abbott Vysis FISH for Xalkori CDx: Ventana ROS Ibrance BRAF... 82

5 Zelboraf (Vemurafenib) Melanoma: Genentech (Roche) Cobas 4800 BRAF V600 Mutation Test Mekinist (Trametinib) in Combination with Tafinlar (Dabrafenib): Novartis THxID-BRAF Kit (biomérieux Inc.) Ventana BRAF V600 (VE1) Antibody BRAF Future Research BCR-ABL for Chronic Myelogenous Leukemia Overview Chronic Myelogenous Leukemia BCR-ABL Gleevec Tests for Gleevec Treatment Gastrointestinal Stromal Tumor CDx: DakoCytomation s c-kit (9.7) pharmdx S ASM and MDS/MPD S CDx: LDTs by ARUP Laboratories BRCA1/ Overview CDx: BRACAnalysis (Myriad Genetics) Immune Checkpoint Inhibitors: Keytruda and Opdivo PD-1 and PD-L1 Inhibitors: Protein Markers CDx: PD-L1 IHC 22C3 pharmdx (Dako) Market Forecast Chapter 6: Current Techniques, Technologies and Market Structures Overview Foundation: Tissue Dx- Histopathology Major Types Of Tissue Diagnostics Hematoxylin & Eosin (H&E) Immunohistochemistry (IHC) In situ Hybridization (ISH) In Practice Used Together Example: Ventana (Roche) Tissue Dx Market Driver: FFPE Compatibility Digital Pathology and Quantitative Immunostaining Future Digital Transformation Imaging Cell Dx: Immunohistochemistry, In Situ Hybridization, DNA, and Quantitative Polymerase Chain Reaction Protein-Based Chromosome-Based DNA-Based mrna-based microrna-based Metabolite-Based Imaging-Based Immunohistochemistry (IHC) Example: Dako (Now Part of Agilent) Practical Application Tissue Context is Key... 98

6 Challenges: Quantification Newer IHC: Quantitative Immunofluorescence (QIF) Future Perspectives Fluorescent In Situ Hybridization Example: Abbott Molecular Diagnostics FISH vs IHC Chromogenic In Situ Hybridization Polymerase Chain Reaction Pros and Cons Discussion Gene Sequencing Overview Functional Genomics Somatic vs Germline Sequencing Tools Used in Functional Genomics History of DNA Sequencing Overview of DNA Sequencing RNA Sequencing Increasing Share Hereditary Cancer Market Leader Trends Current Tests Mostly Single-Target Future: More Multi-gene Panels Novel Panels Drive Growth and Complexity Most Common Genes Included in Myriad of Products Other Sequencing Approaches Other Technologies Recap NGS as a Growth Driver NGS Poised to Dominate Envisioning NGS Panels Enabling New Paradigm: Dx Drives Rx Primer on NGS Platforms FDA-cleared MiSeqDx Clinical Challenges for NGS Standardization Challenges for NGS LDTs: Key Market Structure Background LDT Share of CDx NGS Driving LDTs Regulatory Drivers Stricter Regulation of LDTs Market Response Implications NGS Driving Liquid Biopsy Technology Market Forecast Chapter 7: Not FDA Required Overview FDA-Approved Kits or Tests: 510(k) and PMA Laboratory-developed Tests

7 LDT Share of CDx LDT Advantages Innovation: Panels LDT Industry Structure Regulatory Outlook and Impact Next-Gen Industry Leadership Key Context of Breast Cancer Breast Cancer Industry Overview of Breast Cancer Breast Cancer Tests Drug Pipeline King of Prognostic and Predictive Tests to Guide Treatment Next-Gen Dx Drivers Disease Overview Classification of Breast Cancer Breast Cancer Evaluation Stage of Disease Ductal Carcinoma In Situ Recurrence Oncotype DX Breast Cancer Test Hormone Sensitivity Estrogen Receptor HER2 Type Triple Negative Causes, Incidence and Risk Factors Pathophysiology ER Positive Metastatic Breast Cancer Prevention Overdiagnosis Treatment Overview Cancer Treatment: Local or Systemic Driven by Stage Treatment Guidelines Prognosis after Treatment Hormone Therapy Aromatase Inhibitors Traditional Drugs Overview Chemotherapy Drugs to Control Side Effects of Breast Cancer Treatment Platinum-based Chemotherapy Adjuvant and Neo-Adjuvant Therapy List of FDA-Approved Drugs Targeted Therapies for Breast Cancer Herceptin (Trastuzumab) Avastin Kadcyla: Roche (Genentech) Perjeta: Roche (Genentech) Tykerb (Lapatinib): Novartis

8 HER2 for Other Cancers Unmet Needs CDx for Herceptin Emerging Therapies Triple Negative Breast Cancer PARP Inhibitors BRCA Targeted Olaparib Diagnosis and Trends Screening Early Imaging Tests Mammography Magnetic Resonance Imaging of the Breast Biopsy Fine Needle Aspiration Biopsy Core Needle Biopsy Vacuum-Assisted Biopsies Surgical (Open) Biopsy Laboratory Examination Grades of Breast Cancer Market Drivers Tissue Diagnostics Response to Chemotherapy Genomics Revolution DNA Repair Pathways Treatment Selection Autoimmune Progression (Future) Current Commercial Status Technologies Overview Immunohistochemical Fluorescent In Situ Hybridization Genomic Leading Breast Cancer Genomic Tests Other Genomic Tests Others Mostly LDTs Cancer Prediction Example: BRCA (Myriad) Early Detection/Screening Tests Risk Assessment Tests Discussion Lab-Developed Tests: Outlook Background Stricter Regulation of Lab-Developed Tests Market Response Implications Reimbursement Market Forecast Chapter 8: Emerging Liquid Biopsy Market Overview

9 Phases of Adoption Limitations of Current Disease Diagnosis Limitations of Minimally Invasive Methods Unmet Need: Lung Cancer Example: Roche Diagnostics Example: GeneStrat and VeriStrat by Biodesix Unmet Need: Bladder Cancer Example: Oncocyte Technology Unmet Need: Thyroid Cancer Screening Opportunities Example: Lung Cancer Complement to CT Scanning Example: Oncocyte Huge Increase in Screening Opportunity Technology Overview Earlier Approaches Other Companies Later Approaches Whole Cell Approach Cell-free DNA and Circulating Tumor DNA Additional Applications KRAS Pancreatic: Small but Clearly Defined NSSCLC: Secondary EGFR Mutation KRAS and Response to Anti-EGFR Drugs PD-L1 in Immuno-oncology Example: Biocept Exosomes Pancreatic Cancer Exosomes: Experiment July Market Drivers Shortcomings Unmet: Early Detection Noninvasive Prenatal Testing as Guide for Liquid Biopsy Overview From Noninvasive Prenatal Testing to Maternal Cancers Noninvasive Prenatal Testing Accelerates Cell-Free DNA Reimbursement Strength of Noninvasive Prenatal Testing Companies Recent Venture Funding Noninvasive Prenatal Testing Tests and Leading Companies Patent Pooling High Risk Only, So Far Noninvasive Prenatal Testing Market Outlook Noninvasive Prenatal Testing Plans for Liquid Biopsy Status of Liquid Biopsy Market Regulatory Backdrop Technical Issues Future Outlook Market Forecast Chapter 9: Universal CDx Overview

10 Drivers Rapid Increase in Targeted Therapies Limited and Poor Tissue Quality Physician Difficulty with Complexity Off-Label Prescription Difficulty Integrating into Clinical Practice Increasing Focus on Community Practices Regulatory Challenges Technology Disruption Economic Disincentives Biomarker Challenges Progress from Proteomics Metabolomics Advantage Increasing Molecular and Genomics Driven Existing Single Marker and Gene Panel Approaches Unmet Need for Whole Genome Sequencing Example: NantHealth-GPS Cancer Challenges to Adoption of Comprehensive Molecular Analysis Examples and Initial Adoption Market Forecast Chapter 10: Future Applications: Cardiovascular and Metabolic Disease Overview Applications Planned Myocardial Ischemia and Infarction Exercise Stress Testing Alcohol Septal Ablation Nitric Oxide Metabolic Pathway Anthracycline-induced Cardiotoxicity Atrial Fibrillation Pulmonary Arterial Hypertension Pulmonary Hypertension as Mitochondria Dysfunction Pulmonary Hypertension and Insulin Resistance Atherosclerosis Risk Lipid Profiles Cholesterol Particles Cholesterol Testing Clinical Uses Statins Possible Adverse Drug Reactions Serum Markers Statin Dose Marker Coadministration Metabolization Differences Genetic Variability Lipid Profile Beyond Statins to Multimarker Approach Jupiter Trial Jupiter Expands Statin Use Jupiter Also Raises Diabetes Risk Guidelines

11 Systemic and Vascular Inflammation High-Sensitivity C-Reactive Protein Myeloperoxidase Lipoprotein-Associated Phospholipase-A Advanced Lipid Testing Apolipoprotein B and A1 (ApoA1) Small-Dense LDL Lipoprotein (a) HDL2b Particle Type Companies Offering Advanced Lipid Testing Liposcale Test Primary Care Physicians Cleveland HeartLab Non-fasting Triglycerides Metabolomic Applications Lipidomics Choline Metabolism Acylcarnitines Trimethylamine N-oxide Microflora-derived Choline Metabolites Link with Gut Microflora Diabetes and Prediabetes Insulin Resistance Link with Obesity Not Conclusive Tools to Detect Insulin Resistance Companies Offering Insulin-Resistance Testing Other Insulin-Resistance Testing Branched-Chain Amino Acids: Insulin Resistance via Exercise Stress Testing Branched-Chain Amino Acids and Gastric Bypass Liver Diseases Methylation Deficiency Folate Deficiency Clinical Liver Disease Diagnosis Treatment Research Progress on Non-Alcoholic Fatty Liver Disease One Way Liver Genomics European Association for the Study of the Liver Applications in Liver Research Liver Metabolism Overview Liver Function and Structure Drug-Induced Liver Injury Example: Kiyatec Liver Inflammation Models Example: Hepregen Liver Regeneration Commercial Considerations Laboratory-Developed Tests Market Forecast

12 Chapter 11: Representative Acquisitions and Company Profiles About BCC Research About BCC Research BCC Membership BCC Custom Research

13 List of Tables Summary Table Global Companion Diagnostics Market, by Category, Through 2021 ($ Millions)... 7 Table 1 Novel New Drug Approvals, Table 2 Novel New Drugs and Percentage Personalized Table Newly Approved Medicines Table 4 Potential Markets for Personalized Medicine ($ Billions) Table 5 Examples of Personalized Medicine Tests Table 6 Biomarker Applications (% of R&D Applications) Table 7 Biomarkers Used in Companion Diagnostics Table 8 FDA Designated CDx Table 9 Partial List of FDA Cleared and Approved Tests for CDx Applications Table 10 Partial List of Biomarkers for FDA Cleared and Approved CDx Tests Table 11 Cancer Biomarkers Implemented as FDA CDx VS FDA Cleared/Approved VS LDTS Table 12 Total Tests Cleared or Approved by FDA Since Table 13 Market Shares of Major In Vitro Diagnostics Companies (%) Table 14 Molecular Diagnostics Companies and Representative Revenue, 2013 ($ Millions) Table 15 Market Share of MDX Sectors (%) Table 16 Representative List of CDX Companies Table 17 Pricing for Common Cancer Drugs ($) Table 18 Nine Factors That Influence Companion Diagnostic Development and Adoption Table 19 Established and Emerging CDx Applications Table 20 Tests for Cystic Fibrosis Table 21 G6PD Testing Companies Table 22 CYP Sensitive Drugs Table 23 Global Human Immunodeficiency Virus Drug Market, 2013 and 2018 ($ Billions) Table 24 Companion Diagnostic Tests on the Market for Infectious Diseases, Table 25 Partnerships in the Field of Companion Diagnostics for Infectious Diseases Between Diagnostics and Pharmaceutical Companies, Table 26 Global Market for FDA Cleared/Approved Applications Other Than Cancer, by Category, Through 2021 ($ Millions) Table 27 FDA Designated CDx by Rx Table 28 HER2 CDx Tests FDA Required for Herceptin Table 29 FDA Required EGFR CDx Tests Table 30 FDA Required KRAS CDx Tests Table 31 FDA Required ALK CDx Tests Table 32 FDA Required BRAF CDx Tests Table 33 FDA Required CDx Tests for Gleevec Table 34 FDA Required BRAC1/2 CDx Tests Table 35 Global Market for FDA Cleared/Approved Cancer Applications, by Category, Through 2021 ($ Millions) Table 36 Advantages and Disadvantages of the Most Common Techniques for Companion Diagnostics, Table 37 Global Market for FDA Cleared/Approved Cancer Applications, by Category, Through 2021 ($ Millions) Table 38 Breast Cancer Stages and Specific Diagnosis Table 39 SEER Summary Stage System for Breast Cancer Table 40 Breast Cancer Stages Table 41 Hormone Therapy Types for Breast Cancer

14 Table 42 Hormone Therapy Drugs for Breast Cancer Table 43 Aromatase Inhibitors for Treating Breast Cancer Table 44 Chemotherapy Drugs for Treating Breast Cancer Table 45 Drugs Approved to Treat Breast Cancer Table 46 Targeted Therapeutics for Breast Cancer Table 47 HER2 CDx Tests FDA Required for Herceptin Table 48 Recurrence Rates at Five Years in Patients with Lymph Nodes that are Positive for Cancer (%) Table 49 Five-Year Survival Rates Correlated with Tumor Stage Table 50 Imaging Tests That Determine if Breast Cancer has Spread Table 51 Grades of Breast Cancer Table 52 Myriad Genetics/CDx Partnerships Table 53 IHC and FISH HER2 Tests Table 54 Genetic Tests for Breast Cancer Treatment Table 55 Leading Breast Cancer Genomic Tests Table 56 Gene Expression Profiling Tests Table 57 Laboratories Offering BRCA Tests Table 58 Next-Generation Breast Cancer Tests Table 59 Laboratory-Developed Test Providers Table 60 Global Market for LDT Cancer Applications, by Category, Through 2021 ($ Millions) Table 61 Advantages of Liquid Biopsy Table 62 CTC Phenotype Criteria Used by CellSearch Table 63 Noninvasive Prenatal Testing Adoption Cycle Table 64 Genetic Testing Companies Market Shares (%) Table 65 Recent Venture Funding of Liquid Biopsy Companies Table 66 Global Market for Liquid Biopsy Technology, Through 2021 ($ Millions) Table 67 Universal CDx Companies Table 68 Global Market for Decision Support Tools from Universal CDx Developers, by Category, Through 2021 ($ Millions) Table 69 Global Metabolomics Market, by Biomarker, Through 2020 ($ Millions) Table 70 Representative Acquisitions

15 List of Figures Summary Figure Global Companion Diagnostics Market, by Category, ($ Millions)... 8

16 About BCC Research 2017 BCC Research LLC BIO077C Companion Diagnostics: Technologies and Markets 341

17 About BCC Research With our unparalleled 45-year history, BCC Research provides comprehensive analysis of global market sizing, forecasting and industry intelligence, covering markets where advances in science and technology are improving the quality, standard and sustainability of businesses, economies and lives. BCC Membership From market sizing and forecasts, to opportunity assessments and competitive analyses, our everexpanding library gives you the data, insights and intelligence required to ensure your project is a success. Members benefit from ongoing, unlimited access to the category or collections of their choice, and most membership packages pay for themselves within two to three reports being accessed. Did you buy this report? You may qualify to apply your purchase price towards a full membership. Call 866/ or info@bccresearch.com to request a demo. BCC Custom Research Our experts provide custom research projects to those working to identify new markets, introduce new products, validate existing market share, analyze competition and assess the potential for products to impact existing markets. With impressive academic credentials and broad and deep knowledge of global industrial markets, our independent analysts and consultants develop the facts, figures, analysis and assessments to inform the decisions that will move your company ahead. Confidential inquiries to: custom@bccresearch.com or BCC Research LLC BIO077C Companion Diagnostics: Technologies and Markets 342

18 DISCLAIMER The information developed in this report is intended to be as reliable as possible at the time of publication and is of a professional nature. This information does not constitute managerial, legal or accounting advice, nor should it be considered as a corporate policy guide, laboratory manual or an endorsement of any product, as much of the information is speculative in nature. BCC Research and the author assume no responsibility for any loss or damage that might result from reliance on the reported information or from its use. ISBN: March BCC Research LLC BIO077C Companion Diagnostics: Technologies and Markets 343