乳癌、前立腺癌における大手製薬会社の研究開発戦略

Abstract

Full Title: Triple Analysis: Decoding Big Pharma' s R&D Strategy In Oncology and Special Focus on Breast and Prostate Cancer

In this triple analysis report BioSeeker Group has analyzed three major and intertwined areas of Decoding Big Pharma' s R&D Strategy in Oncology, Breast- and Prostate cancer, which are all subjects to an extensive number of innovative drug candidates. This extensive 440+ 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

In breast cancer we have identified 170 drug candidates in clinical stage of development and more than 100 companies are involved in the development of these drugs. As a treatment for breast cancer hormone modifying therapies together with different chemotherapeutic schedules have been of highest interest during the last years of progress. A vast amount of new clinical research data has emerged and several new clinical trials have been initiated and others generated new results. Protein kinase inhibitors and epothilones have generated substantial amount of new research data in this field. But, other strategies seem not successful and we are still waiting new information regarding their progress.

In prostate cancer we have identified 127 drug candidates in phase II or III stage of development and more than 85 companies are involved in the development of these drugs. Two of the most successful strategies are apoptosis inducers and cell based vaccines. Three out of 10 late stage candidates are apoptosis inducers. Cell based vaccines has been tried for some time but has so far failed to generate substantial improvements.

Breast and Prostate Cancer Highlights

• Thorough examination of status and impact of several novel drugs in development
• Discussion of the challenges in current and future treatment strategies
• Anticancer pipeline of most companies in the field

Key reasons to read this report

• This report serves as a serious reference for professionals interested in the development of oncology drug targets and selection/validation of targeting strategies.
• Explore the strengths and weaknesses associated with compounds in clinical development. Scientific rationale for most novel therapeutics in breast- and prostate cancer R&D, and the results of clinical trials to date
• Gain insight into the current challenges and commercial opportunities associated with breast- and prostate cancer therapy

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 Breast Cancer: An Introduction

• 10.1 Disease Definitions
• 10.2 Etiology
• 10.3 Epidemiology
• 10.4 Prognosis

11 Current Treatment Strategies of Breast cancer

• 11.1 Localized Disease
• 11.2 Advanced Disease

12 Progress in Current Breast Cancer Treatment Strategies

• 12.1 Hormone Based Therapies
• 12.2 Antibodies
• 12.3 Chemotherapy
• 12.4 Chemotherapy

13 Key Therapeutic Strategies for Future Breast Cancer Therapies

• 13.1 Therapeutic Type, Targets & Mechanisms

14 Competitive Landscape in Breast Cancer Drug Development: The Late Stage Pipeline

• 14.1 The Epothilones
• 14.2 Cell Cycle & Apoptosis
• 14.3 Protein Kinase Inhibitors
• 14.4 Immunotherapy

15 Current Drug Development for Breast Cancer: The Early Stage Pipeline

• 15.1 DNA Targeting
• 15.2 FTIs
• 15.3 Antisense
• 15.4 New Hormone Modulators
• 15.5 Other

16 Prostate Cancer: An Introduction

• 16.1 Disease Definitions
• 16.2 Etiology & Pathophysiology
• 16.3 Epidemiology
• 16.4 Prognosis

17 Current Prostate Cancer Treatment Strategies

• 17.1 Localized Disease
  • 17.1.1 Locally Advanced Prostate Cancer
• 17.2 Metastatic Prostate Cancer
  • 17.2.1 Hormone-Sensitive Metastatic Prostate Cancer
  • 17.2.2 Hormone-Refractory or Recurrent Metastatic Prostate Cancer

18 Progress in Current Prostate Cancer Treatment Strategies

• 18.1 Long-Term Follow-up Data not yet Been Published
• 18.2 Significant Reduced Risk of Distant Metastases
• 18.3 Adverse Events
• 18.4 No Difference in Overall Survival
• 18.5 Cross-over Design an Optimal Option?
• 18.6 Death due to Liver Failure
• 18.7 Survival Benefit
• 18.8 Subdermal Implant
• 18.9 No FDA Approval
• 18.10 No Improvement in 5-year Disease-Free Survival
• 18.11 Effective Secondary Hormonal Therapy?
• 18.12 Synery in Combination

19 Key Therapeutic Strategies for Future Prostate Cancer Therapies

• 19.1 Therapeutic Type, Targets & Mechanisms

20 Competitive Landscape in Prostate Cancer Drug Development: The Late Stage Pipeline

• 20.1 Reduced Prostate Cancer Risk
• 20.2 High Activity in Metastatic AIPC Patients
• 20.3 Absence of Severe Toxicities
• 20.4 Waiting for Data
• 20.5 Probability of Regulatory Approval?
• 20.6 Co-development and License Agreement
• 20.7 Improves Predicted Survival?
• 20.8 Slow Progress & Development Partners
• 20.9 Exclusive License Agreement

21 Current Prostate Cancer Drug Development: The Early Stage Pipeline

• 21.1 New Data?
• 21.2 Terminated Study
• 21.3 More Than 50% PSA decline
• 21.4 Safety and Tolerability
• 21.5 Terminated?
• 21.6 Marker of Drug Effect
• 21.7 Preliminary Results for a Tyrosine Kinase Inhibitor
• 21.8 No Activity in Monotherapy
• 21.9 Dramatic Disappearance of Bone Metastatic Lesions
• 21.10 PSA Response - Anthracycline

22 Disclaimer

23 Drug Index

24 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: The Stage System
• Table 106: Risk Factors
• Table 107: List of Approved Drugs and Their Mechanisms of Action.
• Table 108: Hormonal Treatment Strategies
• Table 109: Adjuvant Systemic Treatment Options for Women With Axillary Node-Negative Breast Cancer
• Table 110: Treatment Options for Women With Axillary Node-Positive Breast Cancer
• Table 111: Chemotherapy Drugs and Regimen
• Table 112: Summay of Drugs Involved in Breast Cancer Therapy
• Table 113: Short Facts Tamoxifen
• Table 114: Short Facts Anastrozole
• Table 115: Short Facts Letrozole
• Table 116: Short Facts Exemestane
• Table 117: Short Facts Goserelin
• Table 118: Short Facts Fulvestrant
• Table 119: Short Facts Trastuzumab
• Table 120 Cancer Immunotherapy Strategies
• Table 121: Progress on Ixabepilone
• Table 122: Progress on CCI-779
• Table 123: Progress on Fenretinide
• Table 124: Progress on Lapatinib
• Table 125: Progress on Bevacizumab
• Table 126: Progress on Theratope
• Table 127: Summary of Mid-Stage to Late stage Investigational Agents Under Development
• Table 128: Summary of Breast Cancer Early Stage Pipeline
• Table 129: The TNM System
• Table 130: Lifestyle factors
• Table 131: Historical Summary of Clinical Studies on Patients with Late Stage Disease
• Table 132: Short Facts Abarelix
• Table 133: Short Facts Bicalutamide
• Table 134: Short Facts Carboplatin
• Table 135: Short Facts Docetaxel
• Table 136: Short Facts Mitoxantrone
• Table 137: Short Facts Flutamide
• Table 138: Short Facts Goserelin
• Table 139: Short Facts Histrelin
• Table 140: Short Facts Lanreotide
• Table 141: Short Facts Leuprolide
• Table 142: Short Facts Nilutamide
• Table 143: Short Facts Estramustine
• Table 144: Summary of Recent Clinical Studies on Patients with Late Stage Disease
• Table 145: Ongoing Late Stage Clinical Studies
• Table 146: Cancer Immunotherapy Strategies
• Table 147: Near Term Progress Toremifene
• Table 148: Near Term Progress Bevacizumab
• Table 149: Near Term Progress Oblimersen
• Table 150: Near Term Progress R-flurbiprofen
• Table 151: Near Term Progress APC8015
• Table 152: Near Term Progress Satraplatin
• Table 153: Near Term Progress GVAX
• Table 154: Near Term Progress Exisulind
• Table 155: Summary of Prostate Cancer Late Stage Pipeline
• Table 156: Paclitaxel
• Table 157: Epothilone
• Table 158: Ixabepilone
• Table 159: PTK/ZK
• Table 160: Arsenic trioxide
• Table 161: Retinoic Acid
• Table 162: Imatinib
• Table 163: Bortezomib
• Table 164: Sorafenib
• Table 165: Doxorubicin
• Table 166: Summary of Prostate Cancer Early Stage Pipeline

List of Boxes

• Box 1: Ongoing Phase III Studies Anastrozole
• Box 2: Ongoing Phase III Studies Letrozole
• Box 3: Ongoing Phase III Studies Exemestane
• Box 4: Ongoing Phase III Studies Goserelin
• Box 5: Ongoing Phase III Studies Fulvestrant
• Box 6: Ongoing Phase III Studies Trastuzumab
• Box 7: The TRAIL Receptor family
• Box 8: The Bcl-2 family of proteins
• Box 9: Quick Facts - BMS-247550
• Box 10: Quick Facts - Temsirolimus
• Box 11: Quick Facts - SDX-105
• Box 12: Quick Facts - 4HPR
• Box 13: Quick Facts - Lapatinib
• Box 14: Quick Facts - Bevacizumab
• Box 15: Quick Facts - Theratope
• Box 16: Erlotinib
• Box 17: Gefitinib
• Box 18: Imatinib
• Box 19: Pemetrexed
• Box 20: NX473
• Box 21: Lonafarnib
• Box 22: Tipifarnib
• Box 23: Bortezomib
• Box 24: Arzoxifene
• Box 25: Patupilone
• Box 26: KOS-862
• Box 27: Southwest Oncology Group Study 99-16 Design
• Box 28: TAX 327 Study Design
• Box 29: The TRAIL Receptor family
• Box 30: The Bcl-2 family of proteins
• Box 31: Quick Facts - Toremifene
• Box 32: Quick Facts - Bevacizumab
• Box 33: Quick Facts - Genasense
• Box 34: Quick Facts - R-flurbiprofen
• Box 35: Quick Facts - Provenge
• Box 36: Quick Facts - Satraplatin
• Box 37: Quick Facts - GVAX
• Box 38: Quick Facts - Exisulind
• Box 39: Quick Facts - Vapreotide
• Box 40: Quick Facts - DCVax