Small Molecule Kinase Inhibitors

Small Molecule Kinase Inhibitors

This report analyzes the Global Market for Small Molecule Kinase Inhibitors in Millions of US$ by the following Product Segments: Gleevec/Glivec, Tarceva, Sutent, Nexavar, Sprycel, Iressa, Tykerb/Tyverb, and Others. Annual forecasts are provided for the period 2006 through 2015. The report profiles 83 companies including many key and niche players worldwide such as Amgen, Inc., Asahi Kasei Pharma Corporation, AstraZeneca plc., Bayer Schering Pharma AG, Bristol-Myers Squibb Company,.Celgene Corporation, Exelixis, Inc., F. Hoffmann-La Roche, Ltd., Chugai Pharmaceutical Co, Ltd., Genentech, Inc., GlaxoSmithKline plc., KAI Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novartis International AG, Onyx Pharmaceuticals, Inc., OSI Pharmaceuticals, Inc., Pfizer, Inc., Takeda Pharmaceutical Company Limited, Millennium Pharmaceuticals Inc, S*Bio Pte Ltd., Sanofi-Aventis, Vertex Pharmaceuticals Incorporated, and Wyeth. Market data and analytics are derived from primary and secondary research. Company profiles are mostly extracted from URL research and reported select online sources.

I. INTRODUCTION, METHODOLOGY & PRODUCT DEFINITIONS

Study Reliability and Reporting Limitations I-1
Disclaimers I-2
Data Interpretation & Reporting Level I-3
Quantitative Techniques & Analytics I-3
Product Definitions and Scope of Study I-3

II. EXECUTIVE SUMMARY

1. INDUSTRY OVERVIEW II-1
Kinase Inhibitors Industry: A Prelude II-1
Understanding Kinase Inhibitors II-1
Drug Development Interest in Kinase Inhibitors Soars II-1
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) II-2
Protein Kinases As Potential Drug Targets: Opportunities Abound II-2
Kinase Profiling: The Backbone for pKi Drug Development II-2
Developing Kinase Inhibitors II-3
Kinase Inhibitors: Huge Potential Envisaged in the Treatment
of Cancer II-3
Rising Incidences of Cancer & Unmet Treatment Needs: A Prime
Driver II-4
Table 2: Global New Cases Registered and Total number of
Deaths Resulting From Cancer (2007): Breakdown by Male and
Female (In Million) II-4
In the Cancer End-Use Market Growth Fundamentals Get Stronger II-4
Interest in Non-Cancer Therapies Gains TractionII-4
Multi-Targeted Kinase Inhibitors: The Next Frontier II-5
Rising Incidences of Resistance Sparks Interest in
Combination Drug Therapies II-5
Single Vs Multi-Target Kinase Inhibitor Drugs II-6
Tough Regulatory Riders Threaten to Slow Down Number of
Approvals II-6
Spiraling Cost of Next Generation Cancer Drugs: A Cause for
Concern II-7
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 II-8
Adequate Reimbursements: Critical to Product Success in the
Marketplace II-8
The Truth Behind Inadequate Reimbursement of New Cancer Drugs II-8
Manufacturers Find Risk-Sharing, Rebating, & Contracting As
Effective Antidotes II-9
Financial-based Contracts II-10
Performance-based Contracts II-10
Reimbursements Issues in UK II-10
On Cards: Reimbursement for Pfizer’s Sutent in UK II-10
Reimbursement for GlaxoSmithKline’s Tyverb Hits a Roadblock
in UK II-10
Reimbursements Issues in the United States II-10
Medicare Shifts Oral Anti Cancer Drugs to Higher Drug
Formulary Tiers II-10
Implications for the Patient II-11
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) II-12

Table 5: Oral Anticancer Drugs Covered in Medicare Part D
Plans (2009): Breakdown of Cost Sharing Range by Drug
Brand II-12

Table 6: Placement of Select Oral Anticancer Drugs in the
Drug Tier System Covered in Medicare Part D Plans for the
Year 2009) II-13
Transition of Oral Anti-Cancer Drugs to Higher Cost Sharing
Tiers: Gleevec A Case in Point: II-13
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) II-13

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) II-14
Emergence of Newer Side effects: An Area of Concern for
Modern pKis II-14
Hsp90 Inhibitors: Hope for Cancer Patients Resistant to
Kinase Inhibitor Drugs II-14
Noteworthy Issues Related to Major Drugs: An Evaluation of
Pros and Cons II-15
Tussle Between Tasigna and Sprycel, to Break Into the
Gleevec Empire II-15
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) II-16
Challenges Ahead for Tykerb II-16
Nexavar Shows Promise in the HCC Market II-17
Key Statistical Findings II-18
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) II-18

Table 11: Tykerb Market (2009 & 2015): Percentage Breakdown
of Dollar Sales by Region - US, Europe and Rest of World
(includes corresponding Graph/Chart) II-18

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) II-19

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) II-19

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) II-20

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) II-20

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) II-21

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) II-21
Outlook II-22
Future Directions: The Shape of Things to Come II-22
Spotlight On HER3 Kinase Inhibitors to Overcome Resistance
to EGFR & HER2 Kinase Inhibitors II-22
Ras-Raf-MEK-ERK: A New Kinase Pathway to Achieve Cell Cycle
Arrest II-22
Key Small Molecule pKis Under Different Stages of Clinical
Trials II-23
Pharmaceutical Industry: Review of the Present Scenario II-25
Developing Countries Hold the Key to Future Growth II-25
Table 18: World Pharmaceutical Industry (2007): BRIC Nations
(Brazil, Russia, India and China), & United States Ranked by
Percentage Growth (includes corresponding Graph/Chart) II-26
Consolidation Gets Underway II-26
Landmark Deals Announced or Completed by Pharma and Biotech
Companies Engaged in Developing Kinase Inhibitor Drugs,
During the Year 2008 & 2009 II-27
Impact of the Recession: An Unequivocal ReviewII-27
Recession Brings Drug Development Efforts Under Siege II-27
Biotech Bankruptcies: Casualties On the Rise II-28

2. KINASE INHIBITOR DRUGS: AN OVERVIEW II-29
Small Molecule Kinase Inhibitors: A Definition II-29
Imatinib (Gleevec®, Glivec® - Novartis) II-29
Approvals II-29
Approvals Pending II-29
Erlotinib (Tarceva® - OSI Pharmaceuticals/ Genentech/ Roche) II-29
Approvals II-30
Approvals pending II-30
Related Clinical Trials II-30
Sunitinib (Sutent® - Pfizer) II-30
Approvals II-30
Related Clinical Trials II-31
Sorafenib (Nexavar™ - Bayer / Onyx)II-31
Approvals II-31
Related Clinical Trials II-31
Dasatinib (SPRYCEL® - Bristol-Myers Squibb) II-32
Approvals II-32
Gefitinib (Iressa® - AstraZeneca) II-32
Iressa®: A Controversial Anti-Cancer Drug II-32
Approvals II-33
Approvals Pending II-33
Related Clinical Trials II-33
Key Ongoing Clinical Trials on Iressa II-33
Lapatinib (Tyverb® / Tykerb® - Glaxo SmithKline) II-33
Approvals II-34
Related Clinical Trials II-34
Temsirolimus (TORISEL™ - Wyeth) II-34
Approvals II-34
Rapamycin (Rapamune® - Wyeth) II-34
Approvals II-34
Nilotinib (Tasigna® - Novartis) II-34
Approvals II-35
Approvals Pending II-35
Related Clinical Trials II-35
Everolimus (Afinitor® - Novartis) II-35
Approvals II-35
Approvals Pending II-35
Related Clinical Trials II-35
Small Molecule Kinase Inhibitor Drugs In Pipeline II-36
Pazopanib (Glaxo SmithKline) II-36
Approvals Pending II-36
Related Clinical Trials II-36
Vandetanib (Zactima® - AstraZeneca) II-36
Related Clinical Trials II-36
Cediranib (Recentin™ - AstraZeneca) II-37
Related Clinical Trials II-37
Ridaforolimus (Merck/ ARIAD) II-37
Related Clinical trials II-37
Bosutinib (Wyeth) II-38
Related Clinical Trials II-38
Alvocidib (Sanofi-Aventis) II-38
Related Clinical Trials II-38
Motesanib (Amgen/ Takeda) II-38
Related Clinical Trials II-38
CP-690550 (Pfizer) II-39
Related Clinical Trials II-39

3. KINASE INHIBITORS: A RUDIMENTARY OVERVIEW II-40
Kinase Inhibitors: A Definition II-40
Kinase Inhibitors Vs Monoclonal Antibodies (mAbs): A Comparison II-40
Comparison of Various Pharmacological and Pharmacokinetic
Parameters For Small Molecules and Monoclonal Antibodies II-41
Types of Protein Kinase Inhibitors: A Classification II-41
Receptor Tyrosine Kinase (RTK) Inhibitors II-42
EGFR (Epidermal Growth Factor Receptor) Inhibitors II-42
HER2 Inhibitors II-42
VEGF (Vascular Endothelial Growth Factor) Inhibitors II-42
FLT3 (Fms-like tyrosine kinase 3) Inhibitors II-43
Non- Receptor Tyrosine Kinase Inhibitors II-43
BCR-Abl Kinase Inhibitors II-43
Src Kinase Inhibitors II-43
Janus (JAK) Kinase Inhibitors II-44
Serine-Threonine Kinase InhibitorsII-44
mTOR (Mammalian Target of Rapamycin) Inhibitors II-44
Rho Kinase Inhibitors II-44
CDK (Cyclin Dependent Kinase) Inhibitors II-45
Protein Kinase C (PKC) InhibitorsII-45
PI3K (Phosphatidylinositol-3-Kinase) Inhibitors II-45
Aurora Kinase Inhibitors II-45
MAP (Mitogen activated protein) / MEK Inhibitors II-46
JNK (C-JUN N-TERMINAL KINASE) INHIBITORS II-46
Others II-46

4. PRODUCT LAUNCHES II-47
KAI Initiates Third Phase Iia Trial for KAI-1678 II-47
SuperGen Discovers a New Class of Kinase Inhibitors II-47
AVEO Joins Hands with Biogen to Develop and Market ErbB3-
Targeted AntibodiesII-47
AVEO Identifies New Indication for AV-951 Triple VEGF
Receptor Inhibitor II-48
GPC Biotech Demonstrates Role of Kinase Inhibitor in Multiple
Myeloma Treatment II-48
MD Biosciences and PharmaGap Join Hands II-48
New JAK Inhibitor Drug from Pfizer Enters Phase III Trial II-48
Millennium Commences Phase II Trials for MLN8237 II-49
Astex Therapeutics Develops Structure of Cyclin Dependent
Kinase 4 II-49
Astex Teams up with Cancer Research UK on Clinical Trials of
AT9283 II-49
Astex Presents AT7519, a Cyclin Dependent Kinase Inhibitor II-49
Cell Biosciences Unveils First Kits for Oncoprotein Analysis II-50
Plexxikon Partners with Roche to Develop and Commercialize
PLX5568 II-50
OSI Applies Additional NDA for Tarceva II-50
KAI and BMS Forms Global Alliance on KAI-9803 II-51
Kosan Biosciences Commences Phase II Trial for Alvespimycin II-51
Plexxikon Announces Commencement of Phase 1 PLX5568 Trial II-51
Exelixis Instigates Phase III XL184Trial II-51
Oncothyreon Commences Phase I PX-866 Clinical Trial II-52
Iressa As Efficient as Chemotherapy for Lung Cancer II-52
Iressa Proves Useful for Non-smoker Patients II-52
GPC Biotech Commence Enrollment in Phase 1 RGB-286638 Trial II-52
AVEO Commences Phase I Clinical Trials of AV-951 II-52
Onyx and Bayer Secure FDA and EC Approval for Nexavar® II-53
Product Patent Application for Iressa Rejected II-53
OSI Pharmaceuticals to Launch Tarceva® in JapanII-53
New Plk1 Kinase Inhibitor BI 2536 Developed II-54
Kinex Files IND Application for KX2-391 II-54
Wyeth Receives FDA Approval for TORISEL for Advanced Renal
Cancer Treatment II-54
Nexavar Gets Approval from Swiss Authorities for Treatment of
Kidney Cancer (Switzerland) II-54

5. RECENT INDUSTRY ACTIVITY II-55
Merck Agrees to Merge with Schering-Plough II-55
Pfizer Agrees to Acquire Wyeth II-55
S*BIO, Tragara Signs Exclusive Agreement II-55
GPC Biotech to Merge with Agennix II-55
Sanofi-Aventis to acquire Bipar Sciences II-56
Pfizer Takes Over Serenex II-56
Roche to Acquire Piramed II-56
Eli Lilly Acquires SGX Pharmaceuticals II-57
Takeda Acquires Millennium II-57
Eli Lilly Acquires ImClone Systems II-57
Antisoma Acquires Xanthus II-58
Cellzome and GSK to Jointly Develop Kinase Inhibitors II-58
Deciphera Pharmaceuticals Partners with Eli Lilly in Oncology
Therapy II-58
ACT Biotech Agrees to Acquire the Under Clinical Stage
Oncology Portfolio of Bayer Healthcare II-59
Cancer Research UK Enters into Clinical Development Agreement
with AstraZeneca II-59
Daiichi and ArQule Enter into Product Development Agreement II-59
Cellzome and GlaxoSmithKline Form Alliance II-60
Emiliem Enters into Agreement with NIH II-60
Astex and Janssen Pharmaceutica Form Alliance II-60
Millipore Launches Tyrosine Kinases Integrated with BioForm
Technology II-60
Aegera Therapeutics Takes over LymphoSign II-61
ARIAD and Merck Collaborate on AP23573 II-61
Invitrogen Form Partnership with Emiliem II-61
Pfizer Collaborate with Rigel, to Develop R343 as Treatment
for Allergic AsthmaII-62

6. FOCUS ON SELECT PLAYERS II-63
Amgen, Inc. (US) II-63
Asahi Kasei Pharma Corporation (Japan) II-63
AstraZeneca plc (UK)II-63
Bayer Schering Pharma AG (Germany) II-63
Bristol-Myers Squibb Company (US) II-64
Celgene Corporation (US) II-64
Exelixis, Inc. (US) II-64
F. Hoffmann-La Roche, Ltd. (Switzerland) II-65
Chugai Pharmaceutical Co, Ltd. (Japan) II-65
Genentech, Inc. (US) II-65
GlaxoSmithKline plc (UK) II-65
KAI Pharmaceuticals, Inc (USA) II-66
Merck & Co., Inc (USA) II-66
Mitsubishi Tanabe Pharma Corporation (Japan) II-67
Novartis International AG (Switzerland) II-67
Onyx Pharmaceuticals, Inc. (US) II-67
OSI Pharmaceuticals, Inc. (US) II-67
Pfizer, Inc. (US) II-68
Takeda Pharmaceutical Company Limited (Japan) II-68
Millennium Pharmaceuticals Inc (USA) II-68
S*Bio Pte Ltd (Singapore) II-69
Sanofi-Aventis (France) II-69
Vertex Pharmaceuticals Incorporated (US) II-69
Wyeth (US) II-70

7. GLOBAL MARKET PERSPECTIVE II-71
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) II-71

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) II-72


III. COMPETITIVE LANDSCAPE

Total Companies Profiled: 83 (including Divisions/Subsidiaries - 95)