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Cancer

Triple Analysis: Non Small Cell Lung Cancer, Protein Kinase Inhibitors & Anti-Angiogenic Agents

 

Publication Date October 2006
Publisher Bioseeker
Product Type Report
Pages 287
ISBN Number not applicable
Product Code BSK00137

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Summary

Executive Summary

In this triple analysis report BioSeeker Group has analyzed three major and intertwined areas of cancer R&D, Non Small Cell Lung Cancer Therapeutics, Protein Kinase Inhibitors and Anti-angiogenesis and Vascular Targeting in Oncology, which are all subjects to an extensive number of innovative drug candidates. This extensive 280+ pages report compiles and analyzes in parallel the progress concerning drug development and competitive situation in the three mentioned key oncology areas. The report will not only provide a framework but also a careful identification and evaluation of drug candidates, technologies and competitors.

Lung cancer is the third most common malignant disease and the first leading cause of cancer death in the western world. The third-generation chemotherapeutic agents have expanded the therapeutic options in the treatment of advanced NSCLC. However, despite their contributions, science has reached a therapeutic plateau. Both Avastin and Efaproxyn have generated exciting data. In this report we are not only describing the progress of different combinations of approved drugs but as well the progress of 21 late stage drug candidates are described and analysed.

NSCLC Highlights:

  • Explore the strengths and weaknesses associated with compounds in clinical development.
  • Scientific rationale for novel therapeutics in lung cancer, and the results of clinical trials to date.
  • Gain insight into the current challenges and commercial opportunities associated with lung cancer
  • The number of protein kinase inhibitor (PKI) drugs has risen sharply, as the number of targets. The fiercest competition in PKI drug development is found in breast, lung, leukemia, prostate, and colorectal cancer. Several big pharma companies are out hunting for promising technology and drugs to complement their internal pipeline.

Protein Kinase Inhibitors in Oncology Highlights:

  • Drugs according to protein kinase target; Dual or multiple kinase inhibitor analysis
  • Targets according to indication
  • Competitive landscape assessment
  • Protein kinase inhibitors on market
  • Thorough review of the seven largest cancer indications in the field of protein kinase inhibitors
  • With Avastin as its bright star, the therapeutic field of anti-angiogenic and vascular targeting drugs in oncology is becoming re-energized. While fragmentation of the oncology market is set to occur as treatment becomes based on tumor growth drivers rather than primary tumor site, the use of targeted therapies, such as anti-angiogenesis, will occur in combination with traditional cytotoxic chemotherapy agents.

Anti-angiogenesis and Vascular Targeting Agents in Oncology Highlights

  • In-depth competitive landscape assessment of the anti-angiogenesis market in oncology
  • Thorough review of utilized targets in anti-angiogenic and vascular target drug development
  • Thorough review of approved drugs
  • Progress analysis of five major cancer indications, including players, drugs, clinical progress and pitfalls

Contents

  • 1 Executive Summary
  • 2 Table of Contents
    • 2.1 List of Boxes
    • 2.2 List of Figures
    • 2.3 List of Tables
  • 3 Methodology
  • 4 Protein Kinase Inhibitors
    • 4.1 Rationale for Development of Kinase Inhibitors in Oncology
    • 4.2 Protein Kinase Targets - A Growing Family
    • 4.3 Challenges in Protein Kinase Drug Discovery
      • 4.3.1 Enabling Structure-Based Drug Design is the Key
      • 4.3.2 Specific Kinase Inhibitors without Kinase Profiling?
    • 4.4 Drugs according to Target
      • 4.4.1 Cyclin-dependent Kinase Target Inhibitors
      • 4.4.2 Aurora Kinase Target Inhibitors
      • 4.4.3 Cell Cycle Checkpoint Target Controls Inhibitors
      • 4.4.4 Tyrosine Kinase Receptor Inhibitors
      • 4.4.5 Other Serine/Threonine Kinase Target Inhibitors
    • 4.5 Dual or Multiple Kinase Inhibitor Analysis
      • 4.5.1 Presentation of Drugs Targeting A to F Kinases
      • 4.5.2 Presentation of Drugs Targeting G to T Kinases
    • 4.6 Targets According to Indication
      • 4.6.1 Breast Cancer
      • 4.6.2 Prostate Cancer: What Cannot be Found in the 'Groins'?
      • 4.6.3 Lung Cancer: A Need for Improved Survival Rates
      • 4.6.4 Colorectal Cancer: EGFR & VEGFR are Strong Targets but There are Others
      • 4.6.5 Leukemia: Show Me the Power of PKI
      • 4.6.6 Melanoma
      • 4.6.7 Lymphoma: We Are In
    • 4.7 Growing Competition in the Field
    • 4.8 Big Pharma Outlook: The Race is On
      • 4.8.1 Novartis Deals - Digs Deeper into Cell Cycle Inhibitors
      • 4.8.2 AstraZeneca - Wheeling and Dealing
      • 4.8.3 Pfizer's Long Look at OSI Pharmaceuticals
      • 4.8.4 GlaxoSmithKline Gains Momentum
    • 4.9 Strategic Deals Creating Competitive Edge
      • 4.9.1 Mergers
      • 4.9.2 Astex - the PKI Switchboard
      • 4.9.3 Big Pharma's Darling
    • 4.10 Current Protein Kinase Inhibitors in Therapy
    • 4.10.1 Mechanism, Target and Developmental History
    • 4.10.2 Approvals: Indications & Markets
    • 4.11 Protein Kinase Inhibitors in Drug Development - A Progress Analysis
    • 4.11.1 Progress Analysis - Breast Cancer
    • 4.11.2 Progress Analysis - Prostate Cancer
    • 4.11.3 Progress Analysis - Lung Cancer
    • 4.11.4 Progress Analysis - Colorectal Cancer
    • 4.11.5 Progress Analysis - Leukemia
    • 4.11.6 Progress Analysis - Melanoma
    • 4.11.7 Progress Analysis - Lymphoma
  • 5 Anti-Angiogenesis & Vascular Targeting
    • 5.1 Neoplastic Angiogenesis & Tumor Vasculature
      • 5.1.1 Tumor Vasculature
      • 5.1.2 The Current Model of Sprouting Angiogenesis
    • 5.2 Main Angiogenic Factors
      • 5.2.1 Vascular Endothelial Growth Factor
      • 5.2.2 The Angiopoietins and Platelet Derived Growth Factor
      • 5.2.3 Integrins in Angiogenesis
      • 5.2.4 Inhibitors of Angiogenesis
    • 5.3 Vascular Targeting Agents
    • 5.4 Vascular Disruptive Agents
    • 5.5 Competitive Landscape in Anti-Angiogenesis and Vascular Targeting in Oncology
    • 5.6 Countries & Players: Who are In the Lead?
      • 5.6.1 Top 10 Players Dominate The Developmental Pipeline
    • 5.7 Deals & Alliances in Anti-Angiogenesis and Vascular Targeting
      • 5.7.1 Review of Deals and Alliances Initiated in 2005
      • 5.7.2 Review of Deals and Alliances Initiated in 2004
      • 5.7.3 Review of Deals and Alliances Initiated in 2003
    • 5.8 Approved Anti-Angiogenic Cancer Drugs: Performance
    • 5.9 Target Analysis in Anti-Angiogenesis and Vascular Targeting
    • 5.10 Targets of Late Stage Anti-Angiogenic Drugs in Development
    • 5.10.1 Drugs with Epidermal Growth Factor Receptor as a Target
    • 5.10.2 Drugs with FMS-related Tyrosine Kinase 1 as a Target
    • 5.10.3 Drugs with FMS-related Tyrosine Kinase 4 as a Target
    • 5.10.4 Drugs with Kinase Insert Domain Receptor as a Target
    • 5.10.5 Drugs with Phosphodiesterase 2A, cGMP-stimulated as a Target
    • 5.10.6 Drugs with Phosphodiesterase 5A, cGMP-specific as a Target
    • 5.10.7 Drugs with Patelet-Derived Growth Factor Receptor, alpha Polypeptide as a Target
    • 5.10.8 Drugs with Platelet-Derived Growth Factor, beta Polypeptide as a Target
    • 5.10.9 Drugs with Protein Kinase C, beta 1 as a Target
    • 5.10.10 Drugs with Ret Proto-Oncogene as a Target
    • 5.10.11 Drugs with v-kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog as a Target
    • 5.10.12 Drugs with v-raf-1 Murine Leukemia Viral Oncogene Homolog 1 as a Target
    • 5.10.13 Drugs with Vascular Endothelial Growth Factor as a Target
    • 5.11 Anti-Angiogenic Drugs and Their Targets According to Top 5 Cancer Indications
    • 5.11.1 Targets in Breast Cancer
    • 5.11.2 Targets in Colorectal Cancer
    • 5.11.3 Targets in Lung Cancer
    • 5.11.4 Targets in Prostate Cancer
    • 5.11.5 Targets in Renal Cancer
    • 5.12 Anti-angiongenesis and Vascular Targeting Drugs in Development: By Major Indications
    • 5.13 General Drug Developmental Overview
    • 5.14 Progress Analysis - Breast Cancer
    • 5.14.1 Phase I Clinical Development
    • 5.14.2 Phase II Clinical Development
    • 5.14.3 Phase III Clinical Development
    • 5.15 Progress Analysis - Colorectal Cancer
    • 5.15.1 Phase I Clinical Development
    • 5.15.2 Phase II Clinical Development
    • 5.15.3 Phase III Clinical Development
    • 5.16 Progress Analysis - Lung Cancer
    • 5.16.1 Phase I Clinical Development
    • 5.16.2 Phase II Clinical Development
    • 5.16.3 Phase III Clinical Development
    • 5.17 Progress Analysis - Prostate Cancer
    • 5.17.1 Phase I Clinical Development
    • 5.17.2 Phase II Clinical Development
    • 5.17.3 Phase III Clinical Development
    • 5.18 Progress Analysis - Renal Cancer
    • 5.18.1 Phase I Clinical Development
    • 5.18.2 Phase II Clinical Development
    • 5.18.3 Phase III Clinical Development
  • 6 Non Small Cell Lung Cancer
    • 6.1 Current Treatment Strategies
    • 6.2 Disease Definition
    • 6.3 Etiology & Pathophysiology
    • 6.4 Prognosis
    • 6.5 Epidemiology
  • 7 Progress in Current Treatment Strategies
    • 7.1 Improvements Adding Microtubule Inhibitor
    • 7.2 Improvement of Disease Related Symptoms in Elderly Patients
    • 7.3 Toxicity profile favored
    • 7.4 A New Formula
    • 7.5 Monotherapy?
    • 7.6 Failed to Demonstrate a Survival Advantage
    • 7.7 Reduction in Mortality Risk
    • 7.8 Near Term Approved Drugs for the Treatment of NSCLC
    • 7.9 Chemotherapy Drugs off Patent
  • 8 Key Drug Strategies in Lung Cancer
    • 8.1 Apoptosis
    • 8.2 Antiangiogenesis and Antivascular Agents
      • 8.2.1 EGFR and VEGFR as Targets
    • 8.3 Immunotherapy
  • 9 Competitive Landscape in Non Small Cell Lung Cancer Drug Development: The Late Stage Pipeline
    • 9.1 Grade 4 Adverse Events
    • 9.2 No New Remarks
    • 9.3 No significant Effect on Overall Survival
    • 9.4 Bristol Myers Squibb Entered Into a NSCLC Agreement
    • 9.5 Many Uncertainties Remains
    • 9.6 Development Terminated
    • 9.7 Continuing Enrollment
    • 9.8 Apoptotic Inducer
    • 9.9 Fully-human Monoclonal Antibody
    • 9.10 Eagerly Awaiting Data
    • 9.11 Mutations and Response
    • 9.12 Statistically and Clinically Significant Survival Advantage
    • 9.13 Anti-idiotypic Monoclonal Antibody
    • 9.14 Shift in the Development Focus
    • 9.15 Sensitizer
    • 9.16 Treatment in Earlier-stage Cancer Could be More Effective
    • 9.17 Discontinued Radiosensitizer
    • 9.18 Improvement in Chemoradiotherapy
    • 9.19 Progress on HDAC Inhibitors
    • 9.20 Progress Analysis Carboxyamidotriazole
    • 9.21 Chemotherapy Nave Subjects
  • 10 Disclaimer
  • 11 Appendix I: Complete List of Angiogenic and Vascular Target Agents in Development in Oncology
  • 12 Appendix II: Treatment Guide Lines
    • 12.1 References
  • 13 Appendix III: Progress Profiles on Approved Drugs in Lung Cancer
    • 13.1 Docetaxel
    • 13.2 Vinorelbine
    • 13.3 Gemcitabine
    • 13.4 Paclitaxel
    • 13.5 Pemetrexed
    • 13.6 Gefitinib
    • 13.7 Erlotinib
  • 14 Company Index
  • 15 Drug Index
  • List of Boxes
    • Box 1: The Power of Ambit's Kinase Profiling
    • Box 2: Summary Terms of the Exelixis Transaction
    • Box 3: Nexavar's Clinical Data That Lead To Its EMEA Approval Myeloma
    • Box 4: Thalomid Delays Time to Disease Progression in Newly Diagnosed Multiple Myeloma
    • Box 5: Strong Clinical Data Suggests Approval to Market Avastin For The Treatment of Both Breast Cancer and NSCLC
    • Box 6: Avastin Fails to Meet Primary Endpoint in Advanced Pancreatic Cancer
    • Box 7: Business & Market - Cilengitide
    • Box 8: Business & Market - Exherin
    • Box 9: Business & Market - WX-UK1
    • Box 10: Business & Market - Combretastatin A-4 phosphate
    • Box 11: Business & Market - GCS-100LE
    • Box 12: Business & Market - PTK/ZK
    • Box 13: Business & Market - AS-1404
    • Box 14: Business & Market - Phosphomannopentaose sulfate
    • Box 15: Business & Market - Squalamine
    • Box 16: Business & Market - talactoferrin alfa
    • Box 17: Business & Market - ZD-6474
    • Box 18: Business & Market - AP-23573
    • Box 19: Business & Market - Volociximab
    • Box 20: Business & Market - XL-999
    • Box 21: Quick facts on Docetaxel
    • Box 22: Scientific Data on Docetaxel
    • Box 23: Quick Facts - Vinorelbine
    • Box 24: Scientific Data on Vinorelbine
    • Box 25: Quick Facts - Gemcitabine
    • Box 26: Scientific Data on Gemcitabine
    • Box 27: Scientific Data on Pemetrexed
    • Box 28: Quick Facts - Pemetrexed
    • Box 29: Quick Facts - Gefitinib
    • Box 30: Scientific Data on Gefitinib
    • Box 31: Quick Facts - Erlotinib
    • Box 32: Generalized Illustration, Depicting the Key Elements Involved in the Apoptotic Pathways
  • List of Figures
    • Figure 1 Top 10 PKI Drug Developing Companies
    • Figure 2 Clinical Trial Distribution in Breast Cancer for PKI Drugs
    • Figure 3 Clinical Trial Distribution in Prostate Cancer for PKI Drugs
    • Figure 4 Clinical Trial Distribution in Lung Cancer for PKI Drugs
    • Figure 5 Clinical Trial Distribution in Colorectal Cancer for PKI Drugs
    • Figure 6 Clinical Trial Distribution in Leukemia for PKI Drugs
    • Figure 7 Clinical Trial Distribution in Melanoma for PKI Drugs
    • Figure 8: Clinical Trial Distribution in Lymphoma for PKI Drugs
    • Figure 9: Establishment of Blood Supply to Tumors
    • Figure 10: Sprouting Angiogenesis
    • Figure 11: Top 5 Countries in Cancer Angiogenesis and Vascular Targeting Research
    • Figure 12: Top 10 Companies' Clinical Trial Progress in Anti-Angiogenesis and Vascular Targeting
    • Figure 13: Deals & Alliances in Anti-Angiogenesis and Vascular Targeting 2001-2005
    • Figure 14: Annual Sales of Avastin on US and Non US Markets
    • Figure 15: Trial Distribution of the Entire Anti-Angiogenic and Vascular Target Agent Field in Oncology
    • Figure 16: Distribution of Anti-Angiogensis & Vascular Targeting Trials in Breast Cancer
    • Figure 17: Distribution of Anti-Angiogensis & Vascular Targeting Trials in Colorectal
    • Figure 18: Distribution of Anti-Angiogensis & Vascular Targeting Trials in Lung Cancer
    • Figure 19: Distribution of Anti-Angiogensis & Vascular Targeting Trials in Prostate Cancer
    • Figure 20: Distribution of Anti-Angiogensis & Vascular Targeting Trials in Renal Cancer
    • Figure 21: Generalized Illustration, Depicting the Key Elements Involved in the Apoptotic Pathways
  • List of Tables
    • Table 1: Overview of Targets in Commercial Development
    • Table 2: Cyclin-dependent Kinase Targets in Development
    • Table 3: Aurora Kinase Targets in Development
    • Table 4: Cell Cycle Checkpoint Targets in Development
    • Table 5: Epidermal Growth Factor Receptor Targets in Development
    • Table 6: FMS-like tyrosine kinases and their Synonyms
    • Table 7: Fms-related Tyrosine Kinase Targets in Development
    • Table 8: Platelet-derived Growth Factor Receptor Targets in Development
    • Table 9: Kinase Insert Domain Targets in Development
    • Table 10: Drugs in Development Targeting the PI3K/Akt/mTOR pathway
    • Table 11: Drugs in Development Targeting the Ras-Raf-MEK-ERK (ERK) pathway
    • Table 12: Serine/Threonine Kinase Inhibitors in Development
    • Table 13: Protein Kinase Targets in Clinical Trials for Breast Cancer
    • Table 14: Protein Kinase Targets in Clinical Trials for Prostate Cancer
    • Table 15: Protein Kinase Targets in Clinical Trials for Lung Cancer
    • Table 16: Protein Kinase Targets in Clinical Trials for Colorectal Cancer
    • Table 17: Protein Kinase Targets in Clinical Trials for Leukemia
    • Table 18: Protein Kinase Targets in Clinical Trials for Melanoma
    • Table 19: Protein Kinase Targets in Clinical Trials for Lymphoma
    • Table 20: Drugs in Therapy - Mechanism & Targets
    • Table 21: Current and Developmental History of PKI Drugs in Therapy
    • Table 22: Approvals: Indications & Markets
    • Table 23: Top 10 Drugs in Terms of Number of Clinical Trials
    • Table 24: List of Cancer Indications Targeted by Protein Kinase Inhibitors
    • Table 25: PKI Drugs in Development for Breast Cancer
    • Table 26: PKI Drugs in Development for Prostate Cancer
    • Table 27: PKI Drugs in Development for Lung Cancer
    • Table 28: PKI Drugs in Development for Colorectal Cancer
    • Table 29: PKI Drugs in Development for Leukemia
    • Table 30: PKI Drugs in Development for Melanoma
    • Table 31: PKI Drugs in Development for Lymphoma
    • Table 32: Top 10's Anti-angiogenic and Vascular Targeting Pipeline Drugs
    • Table 33: Deals & Alliances in 2005
    • Table 34: Deals & Alliances in 2004
    • Table 35: Deals & Alliances in 2003
    • Table 36: Companies with Cancer Anti-angiogenic Drugs on the Market
    • Table 37: 2006 Q2 Sales Revlimid and Thalomid
    • Table 38: 2006 Q2 Sales of Avastin
    • Table 39: List of 75 Known Targets in Ant-angiogenis and Vascular Targeting in Drug Development
    • Table 40: Known Targets of Late Stage Anti-Angiogenic Drugs in Development
    • Table 41: Drugs with Epidermal Growth Factor Receptor as a Target
    • Table 42: Drugs with FMS-related Tyrosine Kinase 1 as a Target
    • Table 43: Drugs with FMS-related Tyrosine Kinase 4 as a Target
    • Table 44: Drugs with Kinase Insert Domain Receptor as a Target
    • Table 45: Drugs with Phosphodiesterase 2A, cGMP-stimulated as a Target
    • Table 46: Drugs with Phosphodiesterase 5A, cGMP-specific as a Target
    • Table 47: Drugs with Patelet-Derived Growth Factor Receptor, alpha Polypeptide as a Target
    • Table 48: Drugs with Platelet-Derived Growth Factor, beta Polypeptide as a Target
    • Table 49: Drugs with Protein Kinase C, beta 1 as a Target
    • Table 50: Drugs with Ret Proto-Oncogene as a Target
    • Table 51: Drugs with v-kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog as a Target
    • Table 52: Drugs with v-raf-1 Murine Leukemia Viral Oncogene Homolog 1 as a Target
    • Table 53: Drugs with Vascular Endothelial Growth Factor as a Target
    • Table 54: Breast Cancer Targets in Anti-Angiogenic Drug Development
    • Table 55: Colorectal Cancer Targets in Anti-Angiogenic Drug Development
    • Table 56: Lung Cancer Targets in Anti-Angiogenic Drug Development
    • Table 57: Prostate Cancer Targets in Anti-Angiogenic Drug Development
    • Table 58: Renal Cancer Targets in Anti-Angiogenic Drug Development
    • Table 59: Top 10 Cancer Indications in Anti-Angiogenesis and Vascular Targeting Cancer Drugs
    • Table 60: Recent Ceased or Discountinued Phase I to Phase III Anti-angiogenic and Vascular Targeting Drugs
    • Table 61: Overview of Drugs in Phase III Clinical Development
    • Table 62: List of Phase I to Phase III Anti-Angiogenesis and Vascular Targeting Agents in Development for Breast Cancer
    • Table 63: List of Phase I to Phase III Anti-Angiogenesis and Vascular Targeting Agents in Development for Colorectal Cancer
    • Table 64: List of Phase I to Phase III Anti-Angiogenesis and Vascular Targeting Agents in Development for Lung Cancer
    • Table 65: List of Phase I to Phase III Anti-Angiogenesis and Vascular Targeting Agents in Development for Prostate Cancer
    • Table 66: List of Phase I to Phase III Anti-Angiogenesis and Vascular Targeting Agents in Development for Renal Cancer
    • Table 67: Chemotherapeutic Drugs for Treatment of NSCLC
    • Table 69: Vascular Targeting Agents under Development
    • Table 70 EGFR and VEGFR Inhibitors
    • Table 71: FMS-like Tyrosine Kinases and Their Synonyms
    • Table 72: Fms-related Tyrosine Kinase Targets in Development
    • Table 73: Protein Kinase Targets in Clinical Trials for Lung Cancer
    • Table 74 Cancer Immunotherapy Strategies
    • Table 75 Recently Presented Studies - Lapatinib
    • Table 76 Recently Presented Studies - ZD-6474
    • Table 77 Recently Presented Studies - Vinflunine
    • Table 78 Recently Presented Studies - Panitumumab
    • Table 79 Recently Presented Studies - Genasense
    • Table 80 Recently Presented Studies - CSetuximab
    • Table 81 Recently Presented Studies - Bevacizumab
    • Table 82 Recently Presented Studies - Bexarotene
    • Table 83 Recently Presented Studies - Xcytrin