癌、白血病、リンパ腫分野における大手製薬会社の研究開発戦略

Abstract

This is the report for professionals interested to grasp big pharma' s R&D strategy in oncology and at the same time have an extensive R&D overview of the leukemia and lymphoma field. This extensive 500+ pages report compiles and analyzes Deals and alliances, Drug targets, Compound types, Targeted therapy areas, and Selection of cancer indications among the five major pharmaceutical companies in the oncology arena: Bristol-Myers Squibb, GlaxoSmithKline, Hoffmann-La Roche, and Sanofi-Aventis. Between them and together with their respective partners they have more than 250 drugs for the treatment of cancer. In other words, their collective R&D capacity and presence is solid enough to set trends for the entire field of oncology drug development. Beyond trends, all five are fiercely defining their competitive edge and advantage in oncology and that is what this report is about. The collective force of the above research and analysis ' decodes' these five big pharma R&D efforts into strategy revealing and gap filing presentations. Enough to fuel and sustain comparative benchmarking, peer group surveillance, and partnership decisions. The report further give an in depth analysis in two important key oncology areas; Breast- and Prostate cancer. And provide a framework but also a careful identification and evaluation of drug candidates, technologies and competitors.

Decoding Big Pharma' s R&D Strategy in Oncology in numbers:

• Includes references to more than 250 drugs and 600 clinical/preclinical trials
• Addresses the competitive situation on more than 80 different cancer indications, including supportive care indications
• Special focus on Angiogenesis-, Antibody-, Apoptosis-, Protein kinase inhibitor- and Vaccine drugs for the treatment of cancer
• The included competitive landscape between the five big pharma includes more than 200 companies related to cancer drug development
• Last five years of deals and alliances in oncology, including almost a hundred different key deals and alliances
• Target analysis of 119 drug targets in oncology, including molecular function of target, target localization, type of compound for targeting, targets affecting signaling pathways etc
• Drug compound analysis by cancer indications

Gain insight into the current challenges and commercial opportunities associated with leukemia and Lymphoma therapy. Explore the strengths and weaknesses associated with compounds in clinical development. Scientific rationale for most novel therapeutics in leukemia and Lymphoma R&D, and the results of clinical trials to date. Leukemia includes a broad variety of histological separate disorders which make the leukemia market segmented. And even though a high level of unmet medical need, together with its dependence on chemotherapy, leukemia has not historically been the focus of significant R&D investment for emerging drugs in the pharmaceutical industry. In this report, BioSeeker does not only describe and analyze the latest years of progress in four different market segments; CLL, CML ALL and AML, but also provide an insight and framework to understand the complex field of leukemia therapeutics. Provide one of the most comprehensive coverage of the R&D trends to set the future leukemia marketplace. BioSeeker presents both an overview and a detailed description on the progress of key drugs in Phase III and II development, together with general descriptions on drugs and targets. We have identified 85 drug candidates in phase II or III stage of development and more than 50 companies are involved in the development of these drugs.

Lymphoma is a broad term encompassing a variety of cancers of the lymphatic system. The two main groups of lymphoma in humans are Hodgkin' s disease (characterized by the growth of Reed-Sternberg cells) and the non-Hodgkin' s lymphoma (NHL). The lymphoma market is a complex topic and several pitfalls await actors not well prepared. BioSeeker Group will guide thru this field and bring structure and knowledge enables our customers to analyze opportunities. This report will help to answer questions on the subject of additional lymphoma treatments beyond Rituxan.

Already today it is clear that rituximab has generated substantial revenues for the companies involved in its development. A collection of emerging facts suggest that numerous of the new targeted therapies are agents that cannot just be added into treatment regimens with conventional drugs. A few of them might have isolated properties on certain biologic targets that may require to be modulated in particular ways before or after cytotoxic chemotherapy. Among the emerging therapeutic strategies, passive and active immunotherapies have clearly continued to be leading strategies. Small molecule apoptotic inducers and kinase inhibitors are as well in the forefront.

The leukemia and lymphoma scope of this report

• Thorough examination of status and impact of several novel drugs in development
• Discussion of the challenges in current and future treatment strategies

Table of Contents

1 Executive Summary

2 Methodologies

3 Table of Contents

• 3.1 List of Tables
• 3.2 List of Boxes

4 Big Pharma' s R&D Position and Strategy in Oncology: A Summary

• 4.1 Bristol-Myers Squibb
• 4.2 GlaxoSmithKline
• 4.3 Hoffmann-La Roche
• 4.4 Novartis
• 4.5 Sanofi-Aventis

5 Last Five Years of Deals and Alliances in Oncology

• 5.1 Bristol Myers Squibb
  • 5.1.1 Discovery and Lead Molecule Improvements
  • 5.1.2 Adding Image Analysis to Support Clinical Trials and Early Diagnosis
  • 5.1.3 Bladder Cancer and Melanoma Registration Filings are Emminent
  • 5.1.4 The Human Kinome and Cell Cycle Inhibitors
  • 5.1.5 Strategic Priorities in Pipeline Development Leads to Divestments
  • 5.1.6 Erbitux Expansion is Set to Challenge Avastin
• 5.2 GlaxoSmithKline
  • 5.2.1 The Biopharmaceutical Strategy at GSK
  • 5.2.2 Out Goes Classes of Small Molecule Inhibitors
  • 5.2.3 Marketing and Manufacturing Collaborations
  • 5.2.4 Patient Selectionfo r GSK' s Targeted Cancer Therapies
  • 5.2.5 GSK Taping Into Knowledge Databases
  • 5.2.6 Increasing the Oral Bioavailability Cytotoxic Oncology Drugs
  • 5.2.7 Oxford University Helps GSK in India
  • 5.2.8 GSK is Set to Improve Medical Imaging
• 5.3 Hoffmann-La Roche
  • 5.3.1 Roche Builds Center of Excellence for RNAi Therapeutics Discovery
  • 5.3.2 A New Delivery Route for Avastin?
  • 5.3.3 Improving Antibody Drugs
  • 5.3.4 Roche Strengthens Presence in Genomics Research Market
  • 5.3.5 Target Validation
  • 5.3.6 Drug Discovery Collaborations
  • 5.3.7 Marketing
  • 5.3.8 Outlicensing
  • 5.3.9 Size Doesn' t Matter: Genentech' s Goal of Aggressively Pursuing Novel and Innovative Therapies
• 5.4 Novartis
  • 5.4.1 Novartis Acquisition of Chiron: A Major Biopharmaceutical Investment
  • 5.4.2 Protein Kinase Inhibitors
  • 5.4.3 Next Generation Oral Topoisomerase Inhibitor and Telomerase Promotors
  • 5.4.4 Novartis Sells of World-Wide Rights
  • 5.4.5 Biomarker and Proteomics Research
• 5.5 Sanofi-Aventis
  • 5.5.1 Target Screening and Validation
  • 5.5.2 Biologicals
  • 5.5.3 A Short Cut to Success?
  • 5.5.4 Aventis Divests Interest
  • 5.5.5 Recombine My Molecule

6 Competitive R&D Comparison on Oncology Drug Target Level

• 6.1 Target Overview
• 6.2 Head to Head Target Comparison by Molecular Function and Cancer Type
  • 6.2.1 Transmembrane Receptor Protein Tyrosine Kinase Activity Targets
  • 6.2.2 Receptor Activity Targets
  • 6.2.3 G-protein Coupled Receptor Activity Targets
  • 6.2.4 Protein Serine/Threonine Kinase Activity Targets
  • 6.2.5 Transcription Factor Activity Targets
  • 6.2.6 Transmembrane Receptor Activity Targets
  • 6.2.7 Catalytic Activity Targets
  • 6.2.8 Cytokine Activity Targets
  • 6.2.9 Protein-Tyrosine Kinase Activity Targets
  • 6.2.10 Kinase Activity Targets
  • 6.2.11 DNA Topoisomerase Activity Targets
  • 6.2.12 Growth Factor Activity Targets
  • 6.2.13 Ligase Activity Targets
  • 6.2.14 Motor Activity Targets
  • 6.2.15 Structural Constituent of Cytoskeleton Targets
  • 6.2.16 Transporter Activity Targets
  • 6.2.17 Targets According to Miscellaneous Molecular Function Groups
  • 6.2.18 Unclassified or Unknown Molecular Function of Targets
• 6.3 Drug Targets by Target Localization and Compound Type
• 6.4 Targets, Drugs and Cancer Indications Linked to Signaling Pathways
  • 6.4.1 Alpha6 Beta4 Integrin Signaling Pathway
  • 6.4.2 Androgen Receptor Signaling Pathway
  • 6.4.3 B Cell Receptor Signaling Pathway
  • 6.4.4 EGFR1 Signaling Pathway
  • 6.4.5 Hedgehog Signaling Pathway
  • 6.4.6 ID Signaling Pathway
  • 6.4.7 IL-1 Signaling Pathway
  • 6.4.8 IL-2 Signaling Pathway
  • 6.4.9 IL-3 Signaling Pathway
  • 6.4.10 IL-4 Signaling Pathway
  • 6.4.11 IL-5 Signaling Pathway
  • 6.4.12 IL-6 Signaling Pathway
  • 6.4.13 IL-9 Signaling Pathway
  • 6.4.14 Kit Receptor Signaling Pathway
  • 6.4.15 Notch Signaling Pathway
  • 6.4.16 T Cell Receptor Signaling Pathway
  • 6.4.17 TGF-beta Receptor Signaling Pathway
  • 6.4.18 TNF-alpha Signaling Pathway
  • 6.4.19 Wnt Signaling Pathway

7 Drug Compound Type Analysis

• 7.1 Deployment of Biological Based Compounds by Cancer Indications
• 7.2 Deployment of Chemical Based Compounds by Cancer Indications
• 7.3 Deployment of Natural Product Compounds by Cancer Indications

8 Drug Development in Oncology by Major Targeted Therapy Areas

• 8.1 Angiogenesis
• 8.2 Antibodies
• 8.3 Apoptosis
• 8.4 Protein Kinase Inhibitors
• 8.5 Vaccines

9 Cancer Indication Focus Analysis

• 9.1 Preclinical Stage Pipeline
• 9.2 Phase I Clinical Stage Pipeline
• 9.3 Phase II Clinical Stage Pipeline
• 9.4 Phase III Clinical Stage Pipeline
• 9.5 Drugs Soon to be on the Market
• 9.6 Approved Drugs

10 Leukemia: An Introduction

• 10.1 Leukemia Disease Definitions
  • 10.1.1 The Lymphoid Malignancies
  • 10.1.2 The Myeloid Malignancies
• 10.2 Etiology & Pathophysiology of Leukemia
  • 10.2.1 The Lymphoid Malignancies
  • 10.2.2 The Myeloid Malignancies
• 10.3 Epidemiology of Leukemia
• 10.4 Prognosis of Leukemia
  • 10.4.1 The Lymphoid Malignancies
  • 10.4.2 The Myeloid Malignancies

11 Current Treatment Strategies of Leukemia

• 11.1 The Lymphoid Malignancies
• 11.2 The Myeloid Malignancies

12 Progress in Current Leukemia Treatment Strategies

• 12.1 The Lymphoid Malignancies
• 12.2 The Myeloid Malignancies

13 Key Therapeutic Strategies for Future Leukemia Therapies

• 13.1 Therapeutic type, Targets & Mechanisms

14 Competitive Landscape in Leukemia Drug Development: The Late Stage Pipeline

• 14.1 The Lymphoid Malignancies
• 14.2 The Myeloid Malignancies

15 Current Leukemia Drug Development: The Early Stage Pipeline

16 The Myeloid Malignancies

• 16.1 The Lymphoid Malignancies

17 Lymphoma: An Introduction

• 17.1 Disease Definition
• 17.2 Etiology & Pathophysiology
• 17.3 Epidemiology

18 Current Lymphoma Treatment Strategies

• 18.1 Hodgkin' s Disease
  • 18.1.1 Radiation Therapy
  • 18.1.2 Chemotherapy
  • 18.1.3 Transplantation
  • 18.1.4 Treatment Option Overview
• 18.2 Non-Hodgkin' s Lymphoma
  • 18.2.1 Radiation Therapy
  • 18.2.2 Chemotherapy
  • 18.2.3 Immunotherapy
  • 18.2.4 Bone Marrow and Peripheral Blood Transplants Watch and Wait
  • 18.2.5 Treatment Option Overview
• 18.3 Prognosis
  • 18.3.1 Hodgkin' s Disease
  • 18.3.2 Non-Hodgkin

19 Progress in Current Lymphoma Treatment Strategies

• 19.1 HODGKIN
• 19.2 NON-HODGKIN
• 19.3 Rituxan
• 19.4 Bexxar
• 19.5 Zevalin

20 Key Therapeutic Lymphoma Strategies

• 20.1 Antibodies & Immunostimulation
• 20.2 Small molecules: Apoptosis inducers & Kinase inhibitors

21 Competitive Landscape in Lymphoma Drug Development: The Late Stage Pipeline

22 Current Lymphoma Drug Development: The Early Stage Pipeline

23 Appendix I: Antibody Targets by Companies

24 Appendix II: Drugs Approved for the Treatment of Leukemia: A Historical Perspective

25 Appendix III: Selected Companies - Anticancer Pipelines

• Accentia BioPharmaceuticals
• Biogen Idec
• Cell Therapeutics
• Cephalon
• Chiron Corporation (Now Novartis)
• Eli Lilly
• Favrille
• Genentech
• Genitope Corporation
• Genmab
• Genta
• GlaxoSmithKline
• Immunomedics
• Inex Pharmaceuticals
• Millennium Pharmaceuticals
• Protein Design Labs
• Roche
• Sanofi-Aventis
• Seattle Genetics
• Wyeth

26 Disclaimer

27 Drug Index

28 Company Index

List of Tables

• Table 1: How to Navigate the Report
• Table 2: Number of Pursued Oncology Drugs Targets by Company
• Table 3: Pursued Oncology Drugs Targets by Molecular Function
• Table 4: Drug Target Expression Profiles in Humans
• Table 5: Identified Targets By Cancer Indications
• Table 6: Head to Head Comparison of Drugs with Transmembrane Receptor Protein Tyrosine Kinase Activity Targets
• Table 7: Head to Head Comparison of Drugs with Receptor Activity Targets
• Table 8: Head to Head Comparison of Drugs with G-protein Coupled Receptor Activity
• Table 9: Head to Head Comparison of Drugs with Protein Serine/Threonine Kinase Activity
• Table 10: Head to Head Comparison of Drugs with Transcription Factor Activity Targets
• Table 11: Head to Head Comparison of Drugs with Transmembrane Receptor Activity Targets
• Table 12: Head to Head Comparison of Drugs with Catalytic Activity Targets
• Table 13: Head to Head Comparison of Drugs with Cytokine Activity Targets
• Table 14: Head to Head Comparison of Drugs with Protein-Tyrosine Kinase Activity Targets
• Table 15: Head to Head Comparison of Drugs with Kinase Activity Targets
• Table 16: Head to Head Comparison of Drugs with DNA Topoisomerase Activity Targets
• Table 17: Head to Head Comparison of Drugs with Growth Factor Activity Targets
• Table 18: Head to Head Comparison of Drugs with Ligase Activity Targets
• Table 19: Head to Head Comparison of Drugs with Motor Activity Targets
• Table 20: Head to Head Comparison of Drugs with Structural Constituent of Cytoskeleton Targets
• Table 21: Head to Head Comparison of Drugs with Transporter Activity Targets
• Table 22: Head to Head Comparison of Drugs with Targets According to Miscellaneous Molecular Function Groups
• Table 23: Head to Head Comparison of Drugs with Unclassified or Unknown Molecular Function Targets
• Table 24: Drug Target Comparison by Target Localization and Compound Type
• Table 25: Targeting Signaling Pathways: An Overview
• Table 26: Targeted Signaling Pathway Profiles of Big Pharma
• Table 27: Targets, Drugs and Cancer Indications Linked to the Alpha6 Beta4 Integrin Signaling Pathway
• Table 28: Targets, Drugs and Cancer Indications Linked to the Androgen Receptor Signaling Pathway
• Table 29: Targets, Drugs and Cancer Indications Linked to the B Cell Receptor Signaling Pathway
• Table 30: Targets, Drugs and Cancer Indications Linked to the EGFR1 Signaling Pathway
• Table 31: Targets, Drugs and Cancer Indications Linked to the Hedgehog Signaling Pathway
• Table 32: Targets, Drugs and Cancer Indications Linked to the ID Signaling Pathway
• Table 33: Targets, Drugs and Cancer Indications Linked to the IL-1 Signaling Pathway
• Table 34: Targets, Drugs and Cancer Indications Linked to the IL-3 Signaling Pathway
• Table 35: Targets, Drugs and Cancer Indications Linked to the IL-4 Signaling Pathway
• Table 36: Targets, Drugs and Cancer Indications Linked to the IL-5 Signaling Pathway
• Table 37: Targets, Drugs and Cancer Indications Linked to the IL-6 Signaling Pathway
• Table 38: Targets, Drugs and Cancer Indications Linked to the Kit Receptor Signaling Pathway
• Table 39: Targets, Drugs and Cancer Indications Linked to the Notch Signaling Pathway
• Table 40: Targets, Drugs and Cancer Indications Linked to the T Cell Receptor Signaling Pathway
• Table 41: Targets, Drugs and Cancer Indications Linked to the TGF-beta Receptor Signaling Pathway
• Table 42: Targets, Drugs and Cancer Indications Linked to the TNF-alpha Signaling Pathway
• Table 43: Targets, Drugs and Cancer Indications Linked to the Wnt Signaling Pathway
• Table 44: Deployment of Biological Based Compounds by Cancer Indications
• Table 45: Deployment of Chemical Based Compounds by Cancer Indications
• Table 46: Deployment of Natural Product Based Compounds by Cancer Indications
• Table 47: Comparative Presentation of Targeted Therapy Areas in Oncology
• Table 48: The Angiogenesis Pipeline by Cancer Type and Developmental Stage
• Table 49: The Antibody Pipeline by Cancer Type and Developmental Stage
• Table 50: The Apoptosis Pipeline by Cancer Type and Developmental Stage
• Table 51: The Protein Kinase Inhibitor Pipeline by Cancer Type and Developmental Stage
• Table 52: The Cancer Vaccine Pipeline by Cancer Type and Developmental Stage
• Table 53: Summary of Big Pharma' s Preclinical Stage Pipeline
• Table 54: Preclinical Stage Pipeline by Cancer Indications
• Table 55: Summary of Big Pharma' s Phase I Clinical Stage Pipeline
• Table 56: : Phase I Clinical Stage Pipeline by Cancer Indications
• Table 57: Summary of Big Pharma' s Phase II Clinical Stage Pipeline
• Table 58: Phase II Clinical Stage Pipeline by Cancer Indications
• Table 59: Summary of Big Pharma' s Phase III Clinical Stage Pipeline
• Table 60: Phase III Clinical Stage Pipeline by Cancer Indications
• Table 61: Oncology Drugs Soon to be on the Market
• Table 62: Summary of Big Pharma' s Approved Oncology Drugs
• Table 63: Approved Drugs by Cancer Indications
• Table 105: ALL Classification
• Table 106: Latest Approved Drugs for the Treatment of Leukemia
• Table 107: Kinase Inhibitors in Development for the Treatment of Leukemia
• Table 108: Near Term Progress Rituximab
• Table 109: Near Term Progress Oblimersen
• Table 110: Near Term Progress Alvocidib
• Table 111: Near Term Progress ATRA
• Table 112: Near Term Progress GVAX
• Table 113: Near Tearm Progress HuM195
• Table 114: Near Term Progress Zarnestra
• Table 115: Near Term Progress Sorafenib
• Table 116: Near Term Progress Valspodar
• Table 117: Summary of Current Late Stage Pipeline
• Table 118: Near Term Progress CEP-701
• Table 119: Near Term Progress PKC412
• Table 120: Near Term Progress SU5416
• Table 121: Near Term Progress PTK787
• Table 122: Near Term Progress VNP40101M
• Table 123: Near Term Progress Troxacitabine
• Table 124: Near Term Progress Decitabine
• Table 125: Near Term Progress Bortezomib
• Table 126: Near Term Progress AG-858
• Table 127: Near Term Progress bevacizumab
• Table 128: Near Term Progress OSI-461
• Table 129: Near Term Progress Xcytrin
• Table 130: Near Term Progress AP23573
• Table 131: Summary of Current Early Stage Pipeline
• Table 132: Drugs used in the treatment of lymphoma.
• Table 133: Summary of Strategies Enhancing Antibody Function
• Table 134: Cancer immunotherapy strategies.
• Table 135: Protein Kinase Targets in Clinical Trials for Lymphoma
• Table 136: Recent published studies Aldesleukin
• Table 137: Recent published studies Arsenic trioxide
• Table 138: Recent published studies BiovaxID
• Table 139: Recent published studies Bortezomib
• Table 140: Recent published studies epratuzumab
• Table 141: Recent published studies FavId
• Table 142: Recent published studies MyVax
• Table 143: Recent published studies Nelarabine
• Table 144: Recent published studies Genasense
• Table 145: Recent published studies Pixantrone
• Table 146: Recent published studies temsirolimus
• Table 147: Recent published studies Zanolimumab
• Table 148: Recent published studies Flavopiridol
• Table 149: Recent published studies bevacizumab
• Table 150: Recent published studies CMC-544
• Table 151: Recent published studies galiximab
• Table 152: Recent published studies LY317615
• Table 153: Recent published studies SGN-40
• Table 154: Recent published studies Apolizumab
• Table 155: Recent published studies SGN-30
• Table 156: Accentia BioPharmaceuticals' Anticancer Pipeline
• Table 157: Biogen-Idec' s Anticancer Pipeline
• Table 158: Cell Therapeutics' Anticancer Pipeline
• Table 159: Cephalon' s Anticancer Pipeline
• Table 160: Chiron' s Anticancer Pipeline
• Table 161: Eli Lilly' s Anticancer Pipeline
• Table 162: Favrille anticancer pipeline
• Table 163: Genentech' s Anticancer Pipeline
• Table 164: Genitope' s Anticancer Pipeline
• Table 165: Genmab' s Anticancer Pipeline
• Table 166: Genta' s Anticancer Pipeline
• Table 167: GlaxoSmithKline' s Anticancer Pipeline
• Table 168: Immunomedics' Anticancer Pipeline
• Table 169: Inex Pharmaceuticals' Anticancer Pipeline
• Table 170: Millennium Pharmaceuticals' Anticancer Pipeline
• Table 171: Protein Design Labs' Anticancer Pipeline
• Table 172: Roche' s Anticancer Pipeline
• Table 173: Sanofi-Aventis anticancer pipeline
• Table 174: Seattle Genetics' Anticancer Pipeline
• Table 175: Wyeth' s Anticancer Pipeline

List of Boxes

• Box 1: Major treatment regimes
• Box 2: CLL staging system
• Box 3: Updated REAL/WHO Classification for B-Cell Neoplasms
• Box 4: Quick Facts - Clofarabine
• Box 5: Quick Facts - Alemtuzumab
• Box 6: Quick Facts - Gemtuzumab
• Box 7: Quick Facts - Imatinib
• Box 8: Quick Facts - Rituximab
• Box 9: Quick Facts - Genasense
• Box 10: Quick Facts - Flavopiridol
• Box 11: Quick Facts - Atra
• Box 12: Quick Facts - Gvax
• Box 13: Quick Facts - Zarnestra
• Box 14: Quick Facts - BAY 43-9006
• Box 15: Quick Facts - Ceplene
• Box 16: Quick Facts - Valspodar
• Box 17: Quick Facts - CEP-701
• Box 18: Quick Facts - PKC412
• Box 19: Quick Facts - SU5416
• Box 20: Quick Facts - PTK787
• Box 21: Quick Facts - Cloretazine
• Box 22: Company statement on progress
• Box 23: Quick Facts - Troxacitabine
• Box 24: Quick Facts - FK228
• Box 25: Quick Facts - Decitabine
• Box 26: Quick Facts - VELCADE
• Box 27: Velcade sales 2005
• Box 28: Quick Facts - AG-858
• Box 29: Quick Facts - Avastin
• Box 30: Quick Facts - OSI-461
• Box 31: Quick Facts - Xcytrin
• Box 32: Quick Facts - AP23573
• Box 33: Possible Complications of Treatment
• Box 34: Updated REAL/WHO Classification for B-Cell Neoplasms
• Box 35: Subclassification of Stage
• Box 36: Updated REAL/WHO Classification for B-Cell Neoplasms
• Box 37: Updated REAL/WHO Classification for T-Cell and Putative NK-Cell Neoplasms
• Box 38: Staging subclassification system
• Box 39: Study details