Small Molecule Kinase Inhibitors

Table of Contents

I. INTRODUCTION, METHODOLOGY & PRODUCT DEFINITIONS

• Study Reliability and Reporting Limitations
• Disclaimers
• Data Interpretation & Reporting Level
• Quantitative Techniques & Analytics
• Product Definitions and Scope of Study

II. EXECUTIVE SUMMARY

1. INDUSTRY OVERVIEW

• Kinase Inhibitors Industry: A Prelude
• Understanding Kinase Inhibitors
• Drug Development Interest in Kinase Inhibitors Soars
• Table 1: Clinical Phase Transition Percentage for Novel Kinase Inhibitor Compounds in Clinical Development - All Drugs Vs Kinase Inhibitors, During the Period (1995-2007) (includes corresponding Graph/Chart)
• Protein Kinases As Potential Drug Targets: Opportunities Abound
• Kinase Profiling: The Backbone for pKi Drug Development
• Developing Kinase Inhibitors
• Kinase Inhibitors: Huge Potential Envisaged in the Treatment of Cancer
• Rising Incidences of Cancer & Unmet Treatment Needs: A Prime Driver
• Table 2: Global New Cases Registered and Total number of Deaths Resulting From Cancer (2007): Breakdown by Male and Female (In Million)
• In the Cancer End-Use Market Growth Fundamentals Get Stronger
• Interest in Non-Cancer Therapies Gains Traction
• Multi-Targeted Kinase Inhibitors: The Next Frontier
• Rising Incidences of Resistance Sparks Interest in Combination Drug Therapies
• Single Vs Multi-Target Kinase Inhibitor Drugs
• Tough Regulatory Riders Threaten to Slow Down Number of Approvals
• Spiraling Cost of Next Generation Cancer Drugs: A Cause for Concern
• Table 3: Average Monthly Costs of Anti-Cancer Drugs (2007): Breakdown of Treatment Costs by Cancer Drug Brands - Rituxan, Erbitux, Revilimid, Avastin - High Dose, Avastin - Low Dose, Nexavar, Sutent, Herceptin, Gleevec, Tarceva, Tykerb, Iressa, Vectibix, Torisel and Targeted Therapies (In US$) for US, EU and Japan
• Adequate Reimbursements: Critical to Product Success in the Marketplace
• The Truth Behind Inadequate Reimbursement of New Cancer Drugs
• Manufacturers Find Risk-Sharing, Rebating, & Contracting As Effective Antidotes
• Financial-based Contracts
• Performance-based Contracts
• Reimbursements Issues in UK
• On Cards: Reimbursement for Pfizer' s Sutent in UK
• Reimbursement for GlaxoSmithKline' s Tyverb Hits a Roadblock in UK
• Reimbursements Issues in the United States
• Medicare Shifts Oral Anti Cancer Drugs to Higher Drug Formulary Tiers
• Implications for the Patient
• Table 4: Oral Anticancer Drugs Covered in Medicare Part D Plans (2009): Percentage Share Breakdown of Plans, Which Require Prior Authorization, & Plans, Which Have Quantity Limits, by Drug Brand (includes corresponding Graph/Chart)
• Table 5: Oral Anticancer Drugs Covered in Medicare Part D Plans (2009): Breakdown of Cost Sharing Range by Drug Brand
• Table 6: Placement of Select Oral Anticancer Drugs in the Drug Tier System Covered in Medicare Part D Plans for the Year 2009)
• Transition of Oral Anti-Cancer Drugs to Higher Cost Sharing Tiers: Gleevec A Case in Point:
• Table 7: Percentage Breakdown of Beneficiaries Prescribed Gleevec and Covered Under Standalone Prescription Drug Plans (PDPs) by Tier For Years 2006 through 2009 (includes corresponding Graph/Chart)
• Table 8: Change in Percentage of Co-insurance Amount for Leading Oral Cancer Therapies Under Standalone Prescription Drug Plans (PDPs) (During 2006 to 2009) - For Gleevec, Tarceva, Sutent, and Tykerb (includes corresponding Graph/Chart)
• Emergence of Newer Side effects: An Area of Concern for Modern pKis
• Hsp90 Inhibitors: Hope for Cancer Patients Resistant to Kinase Inhibitor Drugs
• Noteworthy Issues Related to Major Drugs: An Evaluation of Pros and Cons
• Tussle Between Tasigna and Sprycel, to Break Into the Gleevec Empire
• Table 9: A Review of the Effectiveness of Sprycel and Tasigna in the Treatment of Chronic Myeloid Leukaemia (CML): Percentage Breakdown of Efficiency Levels by Clinical Endpoints As a Measure of Patient Response (includes corresponding Graph/Chart)
• Challenges Ahead for Tykerb
• Nexavar Shows Promise in the HCC Market
• Key Statistical Findings
• Table 10: Global Tykerb Market (2007&2015): Percentage Breakdown of Revenue by Indication - Breast Cancer (HER2 positive) 1st, Breast Cancer (HER2 positive) 2nd, Breast Cancer (HER2 positive) 3rd, Breast Cancer (HER2 positive) Brain, H&N adjuvant, Gastric (HER2 positive) 2nd line and Adjuvant Breast (HER2 positive) (includes corresponding Graph/Chart)
• Table 11: Tykerb Market (2009 & 2015): Percentage Breakdown of Dollar Sales by Region - US, Europe and Rest of World (includes corresponding Graph/Chart)
• Table 12: Global Sales of Iressa in the Treatment of NSCLC (2009E): Percentage Breakdown by First Line NSCLC, Second Line NSCLC and Third Line NSCLC (includes corresponding Graph/Chart)
• Table 13: Global Sales of Nexavar (2009 & 2015P): Percentage Breakdown of Dollar Sales by Indication - Renal Cell Carcinoma, Hepato Cellular Carcinoma, Melanoma, and Non-small Cell Lung Cancer (includes corresponding Graph/Chart)
• Table 14: Global Sales of Nexavar (2009 & 2015P): Percentage Breakdown of Dollar Sales by Geographic Region/Country - United States, Europe, and Rest of World (includes corresponding Graph/Chart)
• Table 15: Global Tarceva Market (2009 & 2015): Percentage Breakdown of Patient Penetration (%) in Treatment of First Line NSCLC, First line Maintenance Therapy following Avastin in NSCLC, Second line NSCLC, and Third line NSCLC, in the US and Rest of World Markets (includes corresponding Graph/Chart)
• Table 16: Canadian Healthcare Market (2007): Breakdown of Total Payments Made by Private and Public Insurers Towards Take Home Cancer Drugs (THCDs) by Select Drug Brands - Gleevec, Tarceva, Sutent, Nexavar, Sprycel, and Iressa (In US$ million) (includes corresponding Graph/Chart)
• Table 17: Canadian Healthcare Market (2007&2008): Percentage Share Breakdown of Patient Claims Made for Small Molecule Kinase Inhibitors by Select Drug Brands - Gleevec, Tarceva, Sprycel, and Tasigna (includes corresponding Graph/Chart)
• Outlook
• Future Directions: The Shape of Things to Come
• Spotlight On HER3 Kinase Inhibitors to Overcome Resistance to EGFR & HER2 Kinase Inhibitors
• Ras-Raf-MEK-ERK: A New Kinase Pathway to Achieve Cell Cycle Arrest
• Key Small Molecule pKis Under Different Stages of Clinical Trials
• Pharmaceutical Industry: Review of the Present Scenario
• Developing Countries Hold the Key to Future Growth
• Table 18: World Pharmaceutical Industry (2007): BRIC Nations (Brazil, Russia, India and China), & United States Ranked by Percentage Growth (includes corresponding Graph/Chart)
• Consolidation Gets Underway
• Landmark Deals Announced or Completed by Pharma and Biotech Companies Engaged in Developing Kinase Inhibitor Drugs, During the Year 2008 & 2009
• Impact of the Recession: An Unequivocal Review
• Recession Brings Drug Development Efforts Under Siege
• Biotech Bankruptcies: Casualties On the Rise

2. KINASE INHIBITOR DRUGS: AN OVERVIEW

• Small Molecule Kinase Inhibitors: A Definition
• Imatinib (Gleevec(r), Glivec(r) - Novartis)
• Approvals
• Approvals Pending
• Erlotinib (Tarceva(r) - OSI Pharmaceuticals/ Genentech/ Roche)
• Approvals
• Approvals pending
• Related Clinical Trials
• Sunitinib (Sutent(r) - Pfizer)
• Approvals
• Related Clinical Trials
• Sorafenib (Nexavar(tm) - Bayer / Onyx)
• Approvals
• Related Clinical Trials
• Dasatinib (SPRYCEL(r) - Bristol-Myers Squibb)
• Approvals
• Gefitinib (Iressa(r) - AstraZeneca)
• Iressa(r): A Controversial Anti-Cancer Drug
• Approvals
• Approvals Pending
• Related Clinical Trials
• Key Ongoing Clinical Trials on Iressa
• Lapatinib (Tyverb(r) / Tykerb(r) - Glaxo SmithKline)
• Approvals
• Related Clinical Trials
• Temsirolimus (TORISEL(tm) - Wyeth)
• Approvals
• Rapamycin (Rapamune(r) - Wyeth)
• Approvals
• Nilotinib (Tasigna(r) - Novartis)
• Approvals
• Approvals Pending
• Related Clinical Trials
• Everolimus (Afinitor(r) - Novartis)
• Approvals
• Approvals Pending
• Related Clinical Trials
• Small Molecule Kinase Inhibitor Drugs In Pipeline
• Pazopanib (Glaxo SmithKline)
• Approvals Pending
• Related Clinical Trials
• Vandetanib (Zactima(r) - AstraZeneca)
• Related Clinical Trials
• Cediranib (Recentin(tm) - AstraZeneca)
• Related Clinical Trials
• Ridaforolimus (Merck/ ARIAD)
• Related Clinical trials
• Bosutinib (Wyeth)
• Related Clinical Trials
• Alvocidib (Sanofi-Aventis)
• Related Clinical Trials
• Motesanib (Amgen/ Takeda)
• Related Clinical Trials
• CP-690550 (Pfizer)
• Related Clinical Trials

3. KINASE INHIBITORS: A RUDIMENTARY

• Kinase Inhibitors: A Definition
• Kinase Inhibitors Vs Monoclonal Antibodies (mAbs): A Comparison
• Comparison of Various Pharmacological and Pharmacokinetic Parameters For Small Molecules and Monoclonal Antibodies
• Types of Protein Kinase Inhibitors: A Classification
• Receptor Tyrosine Kinase (RTK) Inhibitors
• EGFR (Epidermal Growth Factor Receptor) Inhibitors
• HER2 Inhibitors
• VEGF (Vascular Endothelial Growth Factor) Inhibitors
• FLT3 (Fms-like tyrosine kinase 3) Inhibitors
• Non- Receptor Tyrosine Kinase Inhibitors
• BCR-Abl Kinase Inhibitors
• Src Kinase Inhibitors
• Janus (JAK) Kinase Inhibitors
• Serine-Threonine Kinase Inhibitors
• mTOR (Mammalian Target of Rapamycin) Inhibitors
• Rho Kinase Inhibitors
• CDK (Cyclin Dependent Kinase) Inhibitors
• Protein Kinase C (PKC) Inhibitors
• PI3K (Phosphatidylinositol-3-Kinase) Inhibitors
• Aurora Kinase Inhibitors
• MAP (Mitogen activated protein) / MEK Inhibitors
• JNK (C-JUN N-TERMINAL KINASE) INHIBITORS
• Others

4. PRODUCT LAUNCHES

• KAI Initiates Third Phase IIa Trial for KAI-1678
• SuperGen Discovers a New Class of Kinase Inhibitors
• AVEO Joins Hands with Biogen to Develop and Market ErbB3-Targeted Antibodies
• AVEO Identifies New Indication for AV-951 Triple VEGF Receptor Inhibitor
• GPC Biotech Demonstrates Role of Kinase Inhibitor in Multiple Myeloma Treatment
• MD Biosciences and PharmaGap Join Hands
• New JAK Inhibitor Drug from Pfizer Enters Phase III Trial
• Millennium Commences Phase II Trials for MLN8237
• Astex Therapeutics Develops Structure of Cyclin Dependent Kinase 4
• Astex Teams up with Cancer Research UK on Clinical Trials of AT9283
• Astex Presents AT7519, a Cyclin Dependent Kinase Inhibitor
• Cell Biosciences Unveils First Kits for Oncoprotein Analysis
• Plexxikon Partners with Roche to Develop and Commercialize PLX5568
• OSI Applies Additional NDA for Tarceva
• KAI and BMS Forms Global Alliance on KAI-9803
• Kosan Biosciences Commences Phase II Trial for Alvespimycin
• Plexxikon Announces Commencement of Phase 1 PLX5568 Trial
• Exelixis Instigates Phase III XL184Trial
• Oncothyreon Commences Phase I PX-866 Clinical Trial
• Iressa As Efficient as Chemotherapy for Lung Cancer
• Iressa Proves Useful for Non-smoker Patients
• GPC Biotech Commence Enrollment in Phase 1 RGB-286638 Trial
• AVEO Commences Phase I Clinical Trials of AV-951
• Onyx and Bayer Secure FDA and EC Approval for Nexavar(r)
• Product Patent Application for Iressa Rejected
• OSI Pharmaceuticals to Launch Tarceva(r) in Japan
• New Plk1 Kinase Inhibitor BI 2536 Developed
• Kinex Files IND Application for KX2-391
• Wyeth Receives FDA Approval for TORISEL for Advanced Renal Cancer Treatment
• Nexavar Gets Approval from Swiss Authorities for Treatment of Kidney Cancer (Switzerland)

5. RECENT INDUSTRY ACTIVITY

• Merck Agrees to Merge with Schering-Plough
• Pfizer Agrees to Acquire Wyeth
• S*BIO, Tragara Signs Exclusive Agreement
• GPC Biotech to Merge with Agennix
• Sanofi-Aventis to acquire Bipar Sciences
• Pfizer Takes Over Serenex
• Roche to Acquire Piramed
• Eli Lilly Acquires SGX Pharmaceuticals
• Takeda Acquires Millennium
• Eli Lilly Acquires ImClone Systems
• Antisoma Acquires Xanthus
• Cellzome and GSK to Jointly Develop Kinase Inhibitors
• Deciphera Pharmaceuticals Partners with Eli Lilly in Oncology Therapy
• ACT Biotech Agrees to Acquire the Under Clinical Stage Oncology Portfolio of Bayer Healthcare
• Cancer Research UK Enters into Clinical Development Agreement with AstraZeneca
• Daiichi and ArQule Enter into Product Development Agreement
• Cellzome and GlaxoSmithKline Form Alliance
• Emiliem Enters into Agreement with NIH
• Astex and Janssen Pharmaceutica Form Alliance
• Millipore Launches Tyrosine Kinases Integrated with BioForm Technology
• Aegera Therapeutics Takes over LymphoSign
• ARIAD and Merck Collaborate on AP23573
• Invitrogen Form Partnership with Emiliem
• Pfizer Collaborate with Rigel, to Develop R343 as Treatment for Allergic Asthma

6. FOCUS ON SELECT PLAYERS

• Amgen, Inc. (US)
• Asahi Kasei Pharma Corporation (Japan)
• AstraZeneca plc (UK)
• Bayer Schering Pharma AG (Germany)
• Bristol-Myers Squibb Company (US)
• Celgene Corporation (US)
• Exelixis, Inc. (US)
• F. Hoffmann-La Roche, Ltd. (Switzerland)
  • Chugai Pharmaceutical Co, Ltd. (Japan)
  • Genentech, Inc. (US)
  • GlaxoSmithKline plc (UK)
  • KAI Pharmaceuticals, Inc (USA)
  • Merck & Co., Inc (USA)
  • Mitsubishi Tanabe Pharma Corporation (Japan)
  • Novartis International AG (Switzerland)
  • Onyx Pharmaceuticals, Inc. (US)
  • OSI Pharmaceuticals, Inc. (US)
  • Pfizer, Inc. (US)
  • Takeda Pharmaceutical Company Limited (Japan)
  • Millennium Pharmaceuticals Inc (USA)
  • S*Bio Pte Ltd (Singapore)
  • Sanofi-Aventis (France)
  • Vertex Pharmaceuticals Incorporated (US)
  • Wyeth (US)

7. GLOBAL MARKET PERSPECTIVE

• Table 19: World Recent Past, Current & Future Analysis for Kinase Inhibitors by Product Segment - Gleevec/Glivec, Tarceva, Sutent, Nexavar, Sprycel, Iressa, Tykerb/Tyverb and Others Independently Analyzed with Annual Sales Figures in US$ Million for Years 2006 through 2015 (includes corresponding Graph/Chart)
• Table 20: World 10-Year Perspective for Kinase Inhibitors by Product Segment - Percentage Breakdown of Dollar Sales for Gleevec/Glivec, Tarceva, Sutent, Nexavar, Sprycel, Iressa, Tykerb/Tyverb and Others For Years 2006, 2009 & 2015 (includes corresponding Graph/Chart)

III. COMPETITIVE LANDSCAPE