CANCER DRUG DISCOVERIES NON-SMALL CELL LUNG CANCER ... · CANCER DRUG DISCOVERIES NON-SMALL CELL...

CANCER DRUG DISCOVERIES NON-SMALL CELL LUNG CANCER CONTENTS

August 2005 © Espicom Business Intelligence

Cancer Drug Discoveries What the future holds

NON-SMALL CELL LUNG CANCER CONTENTS

NON-SMALL CELL LUNG CANCER (NSCLC) ...............................................................................1

Key bullet points .............................................................................................................................1

BACKGROUND TO NSCLC.............................................................................................................2

What is NSCLC and how does it affect patients? ........................................................................2 Stages of the disease.................................................................................................................................3

Patient statistics..............................................................................................................................4 Incidence, diagnosis rates & treatment; now and in the future ............................................................4

Patient growth drivers ....................................................................................................................5 The addressable NSCLC market will increase by 17% by 2012 ............................................................5

CURRENT TREATMENTS ...............................................................................................................9

CHEMOTHERAPY..........................................................................................................................10 SWOT analysis of chemotherapy ...........................................................................................................12

Strengths ...........................................................................................................................................12 Weaknesses......................................................................................................................................12 Opportunities .....................................................................................................................................12 Threats ..............................................................................................................................................12

SWOT analysis of individual chemotherapy treatments......................................................................12 Taxotere (sanofi-aventis) .........................................................................................................................13

Strengths ...........................................................................................................................................13 Weaknesses......................................................................................................................................13 Opportunities .....................................................................................................................................14 Threats ..............................................................................................................................................14 Sales forecasts..................................................................................................................................14

Taxol (Bristol-Myers Squibb) ...................................................................................................................14 Strengths ...........................................................................................................................................15 Weaknesses......................................................................................................................................15 Opportunities .....................................................................................................................................15 Threats ..............................................................................................................................................15 Sales forecasts..................................................................................................................................16

Navelbine (GlaxoSmithKline)...................................................................................................................16 Strengths ...........................................................................................................................................16

NON-SMALL CELL LUNG CANCER CONTENTS CANCER DRUG DISCOVERIES


Weaknesses ......................................................................................................................................16 Opportunities .....................................................................................................................................16 Threats ..............................................................................................................................................16 Sales forecasts ..................................................................................................................................16

Gemzar (Eli Lilly)......................................................................................................................................17 Strengths ...........................................................................................................................................17 Weaknesses ......................................................................................................................................19 Opportunities .....................................................................................................................................19 Threats ..............................................................................................................................................19 Sales forecasts ..................................................................................................................................19

Alimta (Eli Lilly).........................................................................................................................................19 Strengths ...........................................................................................................................................20 Weaknesses ......................................................................................................................................20 Opportunities .....................................................................................................................................20 Threats ..............................................................................................................................................20 Sales forecasts ..................................................................................................................................20

Novel therapies .............................................................................................................................21

Targeting VEGF.............................................................................................................................22

Targeting EGFr..............................................................................................................................24 Iressa (AstraZeneca)................................................................................................................................25

Strengths ...........................................................................................................................................26 Weaknesses ......................................................................................................................................26 Opportunities .....................................................................................................................................27 Threats ..............................................................................................................................................28 Sales forecasts ..................................................................................................................................29

Tarceva (Roche/Genentech/OSI Pharmaceuticals).................................................................................29 Strengths ...........................................................................................................................................29 Weaknesses ......................................................................................................................................30 Opportunities .....................................................................................................................................30 Threats ..............................................................................................................................................31 Sales forecasts ..................................................................................................................................31

Sales forecast of current NSCLC drugs......................................................................................33

RESEARCH & DEVELOPMENT OF NSCLC DRUGS...................................................................36

Phase II / III drugs of interest .......................................................................................................38

New cytotoxics..............................................................................................................................40 Eloxatin (sanofi-aventis) - Phase III .........................................................................................................40

Strengths ...........................................................................................................................................40 Weaknesses ......................................................................................................................................41 Opportunities .....................................................................................................................................41 Threats ..............................................................................................................................................42 Sales forecasts ..................................................................................................................................42



Telcyta (Telik) - Phase II / III ....................................................................................................................42 Scientific rationale .............................................................................................................................42 Strengths ...........................................................................................................................................44 Weaknesses......................................................................................................................................44 Opportunities .....................................................................................................................................44 Threats ..............................................................................................................................................44 Probability of success and sales forecast .........................................................................................44

Satraplatin (Spectrum Pharmaceuticals/GPC Biotech) - Phase II...........................................................45 Scientific rationale .............................................................................................................................45 Strengths ...........................................................................................................................................45 Weaknesses......................................................................................................................................45 Opportunities .....................................................................................................................................46 Threats ..............................................................................................................................................46 Probability of success and sales forecast .........................................................................................46

Novel therapies..............................................................................................................................47 Erbitux (BMS/Merck KGaA/ImClone) - Phase III .....................................................................................47

Strengths ...........................................................................................................................................47 Weaknesses......................................................................................................................................49 Opportunities .....................................................................................................................................49 Threats ..............................................................................................................................................50 Sales forecasts..................................................................................................................................50

Avastin (Genentech/Roche) - Phase III ...................................................................................................50 Strengths ...........................................................................................................................................51 Weaknesses......................................................................................................................................51 Opportunities .....................................................................................................................................52 Threats ..............................................................................................................................................53 Sales forecasts..................................................................................................................................53

Neovastat (AEterna Zentaris) - Phase III.................................................................................................54 Strengths ...........................................................................................................................................55 Weaknesses......................................................................................................................................55 Opportunities .....................................................................................................................................55 Threats ..............................................................................................................................................55 Probability of success and sales forecast .........................................................................................56

Epidermal growth factor inhibitors.........................................................................................................56 Panitumumab (Amgen) - Phase III ..........................................................................................................56

Filing and sales forecasts..................................................................................................................57 Matuzumab (Merck KGaA) - Phase II......................................................................................................58

Filing and sales forecasts..................................................................................................................58 DNA synthesis inhibitor...........................................................................................................................59

Triapine (Vion/Eli Lilly) - Phase II.............................................................................................................59 Scientific rationale .............................................................................................................................59 Filing and sales forecasts..................................................................................................................60

Cancer vaccines .......................................................................................................................................61



L-BLP25 (Biomira/Merck KGaA) - Phase III.............................................................................................61 Scientific rationale .............................................................................................................................61 Strengths ...........................................................................................................................................62 Weaknesses ......................................................................................................................................62 Opportunities .....................................................................................................................................62 Threats ..............................................................................................................................................62 Filing and sales forecasts..................................................................................................................62

SAI-EGF/SAI-TGF-alpha/SAI-EGFr-ECD (CancerVax) - Phase II / III ....................................................63 Scientific rationale .............................................................................................................................63 Strengths ...........................................................................................................................................64 Weaknesses ......................................................................................................................................64 Opportunities .....................................................................................................................................65 Threats ..............................................................................................................................................65 Filing and sales forecasts..................................................................................................................65

MVA-HPV-IL2 (TG4001; Transgene) - Phase II ......................................................................................65 Strengths ...........................................................................................................................................65 Weaknesses ......................................................................................................................................66 Opportunities .....................................................................................................................................66 Threats ..............................................................................................................................................66 Probability of success and sales forecasts .......................................................................................66

Onconase (Alfacell) Phase I/II .................................................................................................................66 Strengths ...........................................................................................................................................67 Weaknesses ......................................................................................................................................67 Opportunities .....................................................................................................................................68 Threats ..............................................................................................................................................68 Filing and sales forecasts..................................................................................................................68

KRX-0401 (Keryx/AEterna Zentaris) - Phase II .......................................................................................69 Strengths ...........................................................................................................................................69 Weaknesses ......................................................................................................................................69 Opportunities .....................................................................................................................................69 Threats ..............................................................................................................................................70 Probability of success and sales forecasts .......................................................................................70

EP-2101 (Epimmune) - Phase I / II ..........................................................................................................70 Strengths ...........................................................................................................................................70 Probability of success and sales forecasts .......................................................................................71

Alternative approaches............................................................................................................................72 Velcade (J&J/Millennium Pharmaceuticals) - Phase II ............................................................................72

Scientific rationale .............................................................................................................................72 Strengths ...........................................................................................................................................73 Weaknesses ......................................................................................................................................73 Opportunities .....................................................................................................................................73 Threats ..............................................................................................................................................74 Probability of success and sales forecasts .......................................................................................74

Ispinesib (GlaxoSmithKline) - Phase II ....................................................................................................74



Strengths ...........................................................................................................................................74 Weaknesses......................................................................................................................................74 Opportunities .....................................................................................................................................75 Threats ..............................................................................................................................................75 Probability of success and sales forecasts .......................................................................................76

Talabostat (Point Therapeutics) - Phase II ..............................................................................................76 Probability of success and sales forecasts .......................................................................................78

Talotrexin (Hana Biosciences) - Phase I / II ............................................................................................78 Scientific rationale .............................................................................................................................78 Strengths ...........................................................................................................................................79 Weaknesses......................................................................................................................................79 Opportunities .....................................................................................................................................79 Threats ..............................................................................................................................................79 Probability of success and sales forecasts .......................................................................................80

Targretin (Ligand Pharmaceuticals) - Phase III .......................................................................................80 Strengths ...........................................................................................................................................80 Weaknesses......................................................................................................................................80 Opportunities .....................................................................................................................................81 Threats ..............................................................................................................................................81 Probability of success and sales forecasts .......................................................................................81

TRAIL-R1 MAb (Human Genome Sciences Inc/Cambridge Antibody Technology) - Phase I / II ...........82 Scientific rationale .............................................................................................................................82 Strengths ...........................................................................................................................................82 Weaknesses......................................................................................................................................83 Opportunities .....................................................................................................................................83 Threats ..............................................................................................................................................84 Probability of success and sales forecasts .......................................................................................84

New formulations .....................................................................................................................................84 Xyotax (Cell Therapeutics / Chugai / Roche) - Phase III .........................................................................84

Scientific rationale .............................................................................................................................85 Strengths ...........................................................................................................................................87 Weaknesses......................................................................................................................................87 Opportunities .....................................................................................................................................87 Threats ..............................................................................................................................................88 Probability of success and sales forecast .........................................................................................88

DN-101 (Novacea) - Phase I/II ................................................................................................................88 Scientific rationale .............................................................................................................................88 Strengths ...........................................................................................................................................88 Weaknesses......................................................................................................................................88 Opportunities .....................................................................................................................................89 Threats ..............................................................................................................................................89 Probability of success and sales forecast .........................................................................................89



DISCONTINUATION OF NSCLC DRUGS .....................................................................................93

THE MARKET - CURRENT AND FUTURE ...................................................................................94

GLOBAL CANCER MARKET ........................................................................................................94

GLOBAL NSCLC MARKET ...........................................................................................................96

Key companies in the global NSCLC market .............................................................................98 AstraZeneca.............................................................................................................................................98 Bristol-Myers Squibb ................................................................................................................................99 sanofi-aventis .........................................................................................................................................102

Leading NSCLC companies in 2012E...................................................................................................104

BIBLIOGRAPHY ..........................................................................................................................105

GLOSSARY..................................................................................................................................107

APPENDIX 1 - US NSCLC DEMOGRAPHICS 2004-2012 ..........................................................111

APPENDIX 2 - EUROPEAN NSCLC DEMOGRAPHICS 2004-2012...........................................112

APPENDIX 3 - JAPANESE NSCLC DEMOGRAPHICS 2004-2012............................................113

CANCER DRUG DISCOVERIES NON-SMALL CELL LUNG CANCER INDEX OF TABLES


NON-SMALL CELL LUNG CANCER INDEX OF TABLES

Table 1: Stages of NSCLC and survival rates ....................................................................................3 Table 2: Summary of global NSCLC patient population forecasts (2004A-2012E) ............................7 Table 3: Standard NSCLC therapy ...................................................................................................10 Table 4: Platinum-based regimes .....................................................................................................10 Table 5: FDA-approved regimens for advanced NSCLC..................................................................11 Table 6: Doublet regimens ................................................................................................................11 Table 7: EGFr expression in solid tumours.......................................................................................24 Table 8: Clinical development of Iressa ............................................................................................28 Table 9: Ongoing clinical trials with Tarceva.....................................................................................31 Table 10: Tarceva filings and indications..........................................................................................32 Table 11: Global NSCLC sales of new products 2004A-2012E (US$ millions)................................33 Table 12: Products in clinical development for the treatment of NSCLC..........................................36 Table 13: Erbitux clinical development programme in NSCLC.........................................................48 Table 14: Avastin clinical development programme .........................................................................52 Table 15: Ongoing panitumumab clinical trials .................................................................................56 Table 16: Current clinical trial development......................................................................................59 Table 17: Upcoming milestones for talabostat..................................................................................78 Table 18: Global NSCLC sales of new products 2004A-2012E (US$ millions)................................91 Table 19: NSCLC drugs discontinued during development..............................................................93 Table 20: BMS oncology franchise ...................................................................................................99 Table 21: BMS oncology pipeline....................................................................................................100 Table 22: GSK oncology franchise..................................................................................................101 Table 23: GSK oncology pipeline....................................................................................................102 Table 24: sanofi-aventis oncology franchise...................................................................................103 Table 25: sanofi-aventis oncology pipeline .....................................................................................103

NON-SMALL CELL LUNG CANCER INDEX OF CHARTS CANCER DRUG DISCOVERIES


NON-SMALL CELL LUNG CANCER INDEX OF CHARTS

Figure 1: Schematic of the lung...........................................................................................................2 Figure 2: Estimated US cancer deaths (2004) ....................................................................................4 Figure 3: a) Tobaccco use in the US b) trends in cigarette smoking prevalence in the US................5 Figure 4: a) Time to disease progression and b) Overall response rate of NSCLC to Gemzar + cisplatin treatment vs cisplatin alone.................................................................................................17 Figure 5: a) Time to disease progression and b) Overall response rate of NSCLC to Gemzar + cisplatin treatment vs etoposide + cisplatin.......................................................................................18 Figure 6: Angiogenesis is the formation of new blood vessels .........................................................22 Figure 7: Agents targeting the VEGF pathway..................................................................................23 Figure 8: EGFr signal transduction in tumour cells ...........................................................................24 Figure 9: Expected US launch times for new NSCLC products........................................................32 Figure 10: Avastin strong US launch.................................................................................................53 Figure 11: Proposed target enzyme of talabostat .............................................................................76 Figure 12: Mechanism of action of talabostat ...................................................................................77 Figure 13: Global oncology market - US$24 billion (2004) ...............................................................94 Figure 14: Key players in the oncology market (2004)......................................................................95 Figure 15: Global NSCLC market by region 2004 - US$2.8 billion ...................................................96 Figure 16: Global NSCLC market by region 2012 - US$12.7 billion .................................................96 Figure 17: Global NSCLC market by therapy class 2004 - US$2.8 billion........................................97 Figure 18: Global NSCLC market by therapy class 2012 - US$12.7 billion......................................97 Figure 19: Market share of NSCLC players by sales (2004A) ..........................................................98 Figure 20: Market share of NSCLC players by sales (2012E) ........................................................104

CANCER DRUG DISCOVERIES PROSTATE CANCER CONTENTS


PROSTATE CANCER CONTENTS

PROSTATE CANCER (PC) ..........................................................................................................115

Key bullet points .........................................................................................................................115

BACKGROUND TO PC................................................................................................................116

What is PC and how does it affect patients?............................................................................116

Patient statistics..........................................................................................................................118 Incidence, diagnosis rates & treatment; now and in the future ........................................................118

Patient growth drivers ................................................................................................................119 US.............................................................................................................................................................120 Europe .....................................................................................................................................................120 Japan .......................................................................................................................................................121

CURRENT TREATMENTS ...........................................................................................................122 SWOT analysis of radiotherapy treatments.........................................................................................125

Strengths .........................................................................................................................................125 Weaknesses....................................................................................................................................125 Opportunities ...................................................................................................................................126 Threats ............................................................................................................................................126

HORMONAL TREATMENT..........................................................................................................127 SWOT analysis of hormonal treatments ..............................................................................................130


SWOT analysis of individual hormonal treatments ............................................................................131 LHRH agonists........................................................................................................................................131 LHRH antagonists ..................................................................................................................................131 Anti-androgens.......................................................................................................................................131

Zoladex (AstraZeneca) ..........................................................................................................................131 Strengths .........................................................................................................................................131 Weaknesses....................................................................................................................................132 Opportunities ...................................................................................................................................132 Threats ............................................................................................................................................132 Sales forecasts................................................................................................................................132

Lupron (TAP Pharmaceuticals/generics) ...............................................................................................132 Strengths .........................................................................................................................................133 Weaknesses....................................................................................................................................133 Opportunities ...................................................................................................................................133 Threats ............................................................................................................................................133

PROSTATE CANCER CONTENTS CANCER DRUG DISCOVERIES


Sales forecasts ................................................................................................................................133 Eligard (sanofi-aventis/Astellas Pharma) ...............................................................................................133

Strengths .........................................................................................................................................134 Weaknesses ....................................................................................................................................134 Opportunities ...................................................................................................................................134 Threats ............................................................................................................................................134 Sales forecasts ................................................................................................................................134

Viadur (Bayer) ........................................................................................................................................134 Strengths .........................................................................................................................................135 Weaknesses ....................................................................................................................................135 Opportunities ...................................................................................................................................135 Threats ............................................................................................................................................135 Sales forecasts ................................................................................................................................135

Vantas (Valera Pharmaceuticals) ..........................................................................................................136 Strengths .........................................................................................................................................136 Weaknesses ....................................................................................................................................137 Opportunities ...................................................................................................................................137 Threats ............................................................................................................................................137 Sales forecasts ................................................................................................................................137

Plenaxis (Praecis Pharmaceuticals) ......................................................................................................137 Strengths .........................................................................................................................................137 Weaknesses ....................................................................................................................................138 Opportunities ...................................................................................................................................138 Threats ............................................................................................................................................138 Sales forecasts ................................................................................................................................138

Casodex (AstraZeneca) .........................................................................................................................138 Strengths .........................................................................................................................................139 Weaknesses ....................................................................................................................................139 Opportunities ...................................................................................................................................139 Threats ............................................................................................................................................139 Sales forecasts ................................................................................................................................139

CHEMOTHERAPY .......................................................................................................................140 SWOT analysis of chemotherapy..........................................................................................................141

Strengths .........................................................................................................................................141 Weaknesses ....................................................................................................................................141 Opportunities ...................................................................................................................................142 Threats ............................................................................................................................................142

SWOT analysis of individual chemotherapy treatments ....................................................................142 Taxotere (sanofi-aventis) .......................................................................................................................142




Sales forecast..................................................................................................................................143 Sales forecast of current PC drugs ...........................................................................................144

RESEARCH & DEVELOPMENT OF PC DRUGS ........................................................................149 5-alpha reductase inhibitors .................................................................................................................149

Proscar (Merck & Co) and Avodart (GlaxoSmithKline)..........................................................................149 Non-steroidal SORM (selective oestrogen receptor modulator) .......................................................149

Acapodene (GTx Inc).............................................................................................................................149

Phase II / III drugs of interest .....................................................................................................152 Immunotherapy.......................................................................................................................................153 Vaccines ..................................................................................................................................................153

Scientific rationale ...........................................................................................................................153 Provenge (Dendreon) - Phase III...........................................................................................................154

Strengths .........................................................................................................................................154 Weaknesses....................................................................................................................................155 Opportunities ...................................................................................................................................155 Threats ............................................................................................................................................155 Probability of success and sales forecast .......................................................................................155

GVAX (Cell Genesys) - Phase III...........................................................................................................156 Strengths .........................................................................................................................................156 Weaknesses....................................................................................................................................157 Opportunities ...................................................................................................................................157 Threats ............................................................................................................................................157 Probability of success and sales forecast .......................................................................................157

Monoclonal antibodies...........................................................................................................................158 Scientific rationale ...........................................................................................................................158

MLN 2704 (Millennium Pharmaceuticals) - Phase II / III .......................................................................158 Probability of success and sales forecast .......................................................................................158

MDX-010 (Medarex) - Phase II..............................................................................................................158 Probability of success and sales forecast .......................................................................................159

Anti-angiogenesis agents......................................................................................................................159 Scientific rationale ...........................................................................................................................159

Thalidomid (Celgene) - Phase III ...........................................................................................................159 Strengths .........................................................................................................................................160 Weaknesses....................................................................................................................................160 Opportunities ...................................................................................................................................160 Threats ............................................................................................................................................160 Probability of success and sales forecast .......................................................................................160

Actimid (CC4047; Celgene Corporation) - Phase II...............................................................................160 Probability of success and sales forecast .......................................................................................161

ZD4054/ZD6474 (AstraZeneca) - Phase II ............................................................................................161 Gleevec/Glivec (Novartis) - Phase II......................................................................................................161

PROSTATE CANCER CONTENTS CANCER DRUG DISCOVERIES


Gene therapy...........................................................................................................................................161 Scientific rationale ...........................................................................................................................161

Genasense (Genta) - Phase II ...............................................................................................................161 Strengths .........................................................................................................................................162 Weaknesses ....................................................................................................................................162 Opportunities ...................................................................................................................................162 Threats ............................................................................................................................................162 Probability of success and sales forecast .......................................................................................162

Endothelin receptor antagonists ..........................................................................................................162 Scientific rationale ...........................................................................................................................162

Xinlay (Abbott Laboratories) - Phase III .................................................................................................163 Strengths .........................................................................................................................................163 Weaknesses ....................................................................................................................................163 Opportunities ...................................................................................................................................163 Threats ............................................................................................................................................163 Probability of success and sales forecast .......................................................................................163

YM598 (Astellas Pharma) - Phase II......................................................................................................164 Hormonal therapies ................................................................................................................................164

Degarelix (Ferring) - Phase II.................................................................................................................164 Cytotoxics ...............................................................................................................................................164

Satraplatin (GPC Biotech/Spectrum Pharmaceuticals) - Phase III ........................................................164 Scientific rationale ...........................................................................................................................164 Strengths .........................................................................................................................................164 Weaknesses ....................................................................................................................................165 Opportunities ...................................................................................................................................165 Threats ............................................................................................................................................165 Probability of success and sales forecast .......................................................................................165

Vitamin D analogues ..............................................................................................................................165 Scientific rationale ...........................................................................................................................165

DN-101 (Novacea) - Phase II.................................................................................................................165 Probability of success and sales forecast .......................................................................................165

Hectorol (Bone Care International) - Phase II........................................................................................166 Epothilone analogues ............................................................................................................................166

Ixabepilone (BMS-247550; Bristol-Myers Squibb) - Phase III ...............................................................166 Strengths .........................................................................................................................................166 Weaknesses ....................................................................................................................................166 Opportunities ...................................................................................................................................166 Threats ............................................................................................................................................167 Probability of success and sales forecast .......................................................................................167

KOS-862 (Kosan/Roche) .......................................................................................................................167 Selective apoptotic anti-neoplastic drugs (SAAND) ...........................................................................167

OP-461 (OSI Pharmaceuticals) - Phase I/II ...........................................................................................167



Sales forecast of new PC drugs.................................................................................................169

DISCONTINUATION OF DRUGS.................................................................................................171

THE MARKET - CURRENT AND FUTURE..................................................................................173

GLOBAL CANCER MARKET ......................................................................................................173

GLOBAL PC MARKET.................................................................................................................174

Key companies in the PC market...............................................................................................177 AstraZeneca...........................................................................................................................................177 Abbott Laboratories................................................................................................................................177 sanofi-aventis.........................................................................................................................................178

Leading PC companies in 2012E ..........................................................................................................178

BIBLIOGRAPHY...........................................................................................................................179

GLOSSARY ..................................................................................................................................181

APPENDIX 1 - US PC DEMOGRAPHICS 2003-2012..................................................................185

APPENDIX 2 - EUROPEAN PC DEMOGRAPHICS 2003-2012 ..................................................186

APPENDIX 3 - JAPANESE PC DEMOGRAPHICS 2003-2012 ...................................................187

PROSTATE CANCER INDEX OF TABLES CANCER DRUG DISCOVERIES


PROSTATE CANCER INDEX OF TABLES Table 1: TNM classification in prostate cancer ...............................................................................117 Table 2: Prostate cancer management ...........................................................................................117 Table 3: Current hormonal treatments ............................................................................................128 Table 4: Average wholesale price of LHRH agonists/antagonists ..................................................136 Table 5: Global PC sales of new products 2004A-2012E (US$ millions) .......................................148 Table 6: Current PC drugs in clinical development .........................................................................150 Table 7: Sales forecasts of new developmental drugs (2004A-2012E) ..........................................169 Table 8: Potential candidates for prostate cancer discontinued from development .......................171

CANCER DRUG DISCOVERIES PROSTATE CANCER INDEX OF CHARTS


PROSTATE CANCER INDEX OF CHARTS Figure 1: Increase in elderly as a % of populations ........................................................................119 Figure 2: Cancer incidence rates for men - US 1975-2001 ............................................................120 Figure 3: Prostate cancer treatment algorithm................................................................................123 Figure 4: Docetaxel combinations currently in research for HRPC ................................................140 Figure 5: Docetaxel combinations in androgen-dependent prostate cancer ..................................141 Figure 6: Expected US launch timescales for prostate cancer therapeutics ..................................147 Figure 7: Provenge mode of action.................................................................................................154 Figure 8: MDX-010 mechanism of action........................................................................................159 Figure 9: Global oncology market 2004 - US$24 billion..................................................................173 Figure 10: Global PC market by region 2004A - US$2.7 billion......................................................174 Figure 11: Global PC market by region 2012E - US$8.6 billion......................................................175 Figure 12: Global PC market by therapy class 2004 - US$2.7 billion.............................................176 Figure 13: Global PC market by therapy class 2012 - US$8.6 billion.............................................176 Figure 14: Market share of top five PC players by sales (2004A) ..................................................177 Figure 15: Market share of top 6 PC players by sales (2012E) ......................................................178

PROSTATE CANCER INDEX OF CHARTS CANCER DRUG DISCOVERIES


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CANCER DRUG DISCOVERIES BREAST CANCER CONTENTS


BREAST CANCER CONTENTS

BREAST CANCER (BC)...............................................................................................................189


BACKGROUND TO BC................................................................................................................190

What is BC and how does it affect patients?............................................................................190 Risk factors .............................................................................................................................................191 Diagnosis ................................................................................................................................................191 Stages of the disease.............................................................................................................................191


Patient growth drivers ................................................................................................................194 The prevalence of people living with BC will increase by 20% by 2012...........................................194

Drug growth drivers ....................................................................................................................198

CURRENT TREATMENTS ...........................................................................................................199

HORMONAL THERAPY...............................................................................................................201 SWOT analysis of hormonal therapies.................................................................................................204


SWOT analysis of individual hormonal treatments ............................................................................205 Anti-oestrogen drugs.............................................................................................................................206

Nolvadex (AstraZeneca) ........................................................................................................................206 Strengths .........................................................................................................................................207 Weakness........................................................................................................................................207 Opportunities ...................................................................................................................................207 Threats ............................................................................................................................................208 Sales forecasts................................................................................................................................208

Faslodex (AstraZeneca).........................................................................................................................208 Strengths .........................................................................................................................................208 Weaknesses....................................................................................................................................209 Opportunities ...................................................................................................................................209 Threats ............................................................................................................................................209 Sales forecasts................................................................................................................................209

Aromatase inhibitors..............................................................................................................................210 Arimidex (AstraZeneca) .........................................................................................................................211

Strengths .........................................................................................................................................211 Weaknesses....................................................................................................................................212

BREAST CANCER CONTENTS CANCER DRUG DISCOVERIES


Opportunities ...................................................................................................................................212 Threats ............................................................................................................................................213 Sales forecasts ................................................................................................................................213

Femara (Novartis) ..................................................................................................................................213 Strengths .........................................................................................................................................214 Weaknesses ....................................................................................................................................215 Opportunities ...................................................................................................................................215 Threats ............................................................................................................................................216 Sales forecasts ................................................................................................................................217

Aromasin (Pfizer) ...................................................................................................................................217 Strengths .........................................................................................................................................217 Weaknesses ....................................................................................................................................218 Opportunities ...................................................................................................................................218 Threats ............................................................................................................................................218 Sales forecasts ................................................................................................................................218

LHRH antagonists...................................................................................................................................219 Zoladex (AstraZeneca)...........................................................................................................................219


CHEMOTHERAPY .......................................................................................................................221 SWOT analysis of individual chemotherapy treatments ....................................................................222 Taxanes ...................................................................................................................................................222

Taxotere (sanofi-aventis) .......................................................................................................................222 Strengths .........................................................................................................................................223 Weaknesses ....................................................................................................................................224 Opportunities ...................................................................................................................................224 Threats ............................................................................................................................................225 Sales forecasts ................................................................................................................................225

Taxol (Bristol-Myers Squibb)..................................................................................................................225 Strengths .........................................................................................................................................226 Weaknesses ....................................................................................................................................226 Opportunities ...................................................................................................................................226 Threats ............................................................................................................................................227 Sales forecasts ................................................................................................................................227

Abraxane (American Pharmaceutical Partners).....................................................................................227 Scientific rationale ...........................................................................................................................227 Sales forecasts ................................................................................................................................228

Navelbine (GlaxoSmithKline) .................................................................................................................228 Strengths .........................................................................................................................................228 Weaknesses ....................................................................................................................................228



Opportunities ...................................................................................................................................228 Threats ............................................................................................................................................229 Sales forecasts................................................................................................................................229

Cytotoxic agents.....................................................................................................................................229 Ellence (Pfizer).......................................................................................................................................229

Strengths .........................................................................................................................................229 Weaknesses....................................................................................................................................229 Opportunities ...................................................................................................................................230 Threats ............................................................................................................................................230 Sales forecasts................................................................................................................................230

Antimetabolites.......................................................................................................................................230 Xeloda (Roche) ......................................................................................................................................230

Mechanism of action .......................................................................................................................230 Strengths .........................................................................................................................................231 Weaknesses....................................................................................................................................231 Opportunities ...................................................................................................................................231 Threats ............................................................................................................................................232 Sales forecasts................................................................................................................................232

Gemzar (Eli Lily) ....................................................................................................................................232 Strengths .........................................................................................................................................233 Weaknesses....................................................................................................................................233 Opportunities ...................................................................................................................................233 Threats ............................................................................................................................................233 Sales forecasts................................................................................................................................234

IMMUNOTHERAPY ......................................................................................................................235 Herceptin (Roche)..................................................................................................................................235

Scientific rationale ...........................................................................................................................235 Mechanism of action .......................................................................................................................235 Strengths .........................................................................................................................................236 Weaknesses....................................................................................................................................237 Opportunities ...................................................................................................................................237 Threats ............................................................................................................................................239 Sales forecasts................................................................................................................................240

Sales forecast of current BC drugs ...........................................................................................241

RESEARCH & DEVELOPMENT OF BC DRUGS ........................................................................245

Phase II / III drugs of interest .....................................................................................................248 Selective oestrogen receptor modulators ...........................................................................................248

Evista (Eli Lilly) - Phase III .....................................................................................................................249 Strengths .........................................................................................................................................250 Weaknesses....................................................................................................................................250 Opportunities ...................................................................................................................................250 Threats ............................................................................................................................................250



Sales forecasts ................................................................................................................................251 Arzoxifene (Eli Lilly) - Phase III ..............................................................................................................251 Oporia (Pfizer) - Phase III ......................................................................................................................251

New aromatase inhibitors......................................................................................................................251 Atamestane (Intarcia Therapeutics) - Phase II ......................................................................................251


Epothilone analogues ............................................................................................................................253 Ixabepilone (Bristol-Myers Squibb) - Phase III.......................................................................................253

Strengths .........................................................................................................................................253 Weaknesses ....................................................................................................................................254 Opportunities ...................................................................................................................................254 Threats ............................................................................................................................................254 Probability of success and sales forecast .......................................................................................254

Other epothilone analogues in clinical development include............................................................254 R1492 (Roche and Kosan Biosciences) - Phase II................................................................................254 EPO906 (Novartis) - Phase II ................................................................................................................255

Novel targeted approaches ...................................................................................................................255 Anti-angiogenesis agents.......................................................................................................................255

Scientific rationale ...........................................................................................................................255 Avastin (Genentech) - Phase III .............................................................................................................256


Lapatinib (GlaxoSmithKline) - Phase II ..................................................................................................258 Scientific rationale ...........................................................................................................................259 Probability of success and sales forecasts .....................................................................................259

Iressa (AstraZeneca) - Phase II .............................................................................................................260 Mechanism of action........................................................................................................................260 Strengths .........................................................................................................................................260 Weaknesses ....................................................................................................................................260 Opportunities ...................................................................................................................................261 Threats ............................................................................................................................................261 Sales forecasts ................................................................................................................................261

Omnitarg (Roche/Genentech) - Phase II ...............................................................................................262 Probability of success and sales forecasts .....................................................................................262

ZD6474 (AstraZeneca) - Phase II ..........................................................................................................262 CI-1033 (Pfizer) - Phase II .....................................................................................................................263



IMC-111F8 (ImClone Systems) - Phase I..............................................................................................263 Alternative targeted approaches to angiogenesis..............................................................................263

INGN 241 (Introgen Therapeutics) - Phase II ........................................................................................263 Scientific rationale ...........................................................................................................................263 Probability of success and sales forecasts .....................................................................................264

Recombinant human insulin-like growth factor binding protein-3..........................................................264 Probability of success and sales forecasts .....................................................................................264

Cancer vaccines .....................................................................................................................................264 IGN101 (Aphton) - Phase III ..................................................................................................................265

Probability of success and sales forecasts .....................................................................................266 HER2 Protein AutoVac (Pharmexa / GlaxoSmithKline) - Phase II ........................................................266 HER2/neu vaccine (GlaxoSmithKline / Corixa) .....................................................................................267

Probability of success and sales forecasts .....................................................................................267 Alternative approaches to BC treatment...................................................................................268 Multi-drug resistant inhibitors (MDRIs) .....................................................................................................268

Tesmilifene (YM Biosciences) - Phase III ..............................................................................................269 Probability of success and sales forecasts .....................................................................................270

MS-209 (Schering AG) - Phase III .........................................................................................................270 Elacridar (GlaxoSmithKline) - Phase I ...................................................................................................270

Gene therapy................................................................................................................................................271 Scientific rationale ...........................................................................................................................271

Genasense (Genta) ...............................................................................................................................271 Strengths .........................................................................................................................................271 Weaknesses....................................................................................................................................271 Opportunities ...................................................................................................................................271 Threats ............................................................................................................................................272 Probability of success and sales forecast .......................................................................................272

Sales forecast of new BC drugs ................................................................................................273 Diagnostic assays .......................................................................................................................................275 HER2 diagnostics ........................................................................................................................................276

HER2/neu diagnostic testing .................................................................................................................276 Fluorescence in situ hybridisation (FISH) ..............................................................................................276 Chromogenic in situ hybridisation (CISH) .............................................................................................276 InSite HER2/neu kit................................................................................................................................276 “Virtual Cancer Patient” technology - Optimata .....................................................................................277

Future advances in diagnostics............................................................................................................277






GLOBAL BC MARKET ................................................................................................................282

Key companies in the global BC market...................................................................................285 AstraZeneca...........................................................................................................................................285 Roche.....................................................................................................................................................286 sanofi-aventis .........................................................................................................................................286 Bristol-Myers Squibb ..............................................................................................................................288

Leading BC companies in 2012E ..........................................................................................................289

BIBLIOGRAPHY ..........................................................................................................................291

GLOSSARY..................................................................................................................................294

APPENDIX 1 - US BC DEMOGRAPHICS 2003-2012 .................................................................297

APPENDIX 2 - EUROPEAN BC DEMOGRAPHICS 2003-2012 ..................................................298

APPENDIX 3 - JAPANESE BC DEMOGRAPHICS 2003-2012...................................................299

WEBSITE REFERENCES ............................................................................................................301

CANCER DRUG DISCOVERIES BREAST CANCER INDEX OF TABLES


BREAST CANCER INDEX OF TABLES Table 1: TMN classification in BC ...................................................................................................192 Table 2: Summary of patient population forecasts (2003A-2012E) ................................................195 Table 3: Current hormonal therapies ..............................................................................................202 Table 4: Key characteristics of the leading hormonal therapies .....................................................203 Table 5: Patent expiration of leading BC hormonal therapies ........................................................205 Table 6: Chemotherapy combinations currently prescribed in Stage I-III BC.................................221 Table 7: Xeloda clinical trial programme.........................................................................................232 Table 8: Pivotal clinical trials with Herceptin ...................................................................................239 Table 9: Global BC sales 2003A-2012E (US$ millions)..................................................................243 Table 10: Products in clinical development for the treatment of BC ...............................................245 Table 11: SORMs in clinical development for BC ...........................................................................248 Table 12: Angiogenesis drugs in clinical development for BC targeting growth factors .................256 Table 13: Ongoing Avastin clinical trials .........................................................................................257 Table 14: Clinical development of Iressa ........................................................................................261 Table 15: BC vaccines in clinical development...............................................................................265 Table 16: Sales forecasts of new developmental BC drugs US$ millions (2005E-2012E).............273 Table 16: BC drugs discontinued during development ...................................................................278 Table 17: sanofi-aventis oncology franchise...................................................................................287 Table 18: sanofi-aventis oncology pipeline .....................................................................................287 Table 19: BMS oncology franchise .................................................................................................288 Table 20: BMS oncology pipeline....................................................................................................289

BREAST CANCER INDEX OF TABLES CANCER DRUG DISCOVERIES


BREAST CANCER INDEX OF CHARTS

Figure 1: Schematic of the breast ...................................................................................................190 Figure 2a) and 2b): Cancer incidence rates and cancer death rates for women in the US............193 Figure 3: BC market opportunities...................................................................................................194 Figure 4: Schematic of treatment options in BC..............................................................................199 Figure 5: Hormones affecting BC....................................................................................................201 Figure 6: Mode of action of anti-oestrogens....................................................................................206 Figure 7: Mode of action of aromatase inhibitors ............................................................................210 Figure 8: Clinical trial data drives growth of BC products ...............................................................211 Figure 9: Market potential for Femara in extended adjuvant setting...............................................216 Figure 10: a) Time to disease progression and b) overall response rate of MBC to Gemzar treatment .........................................................................................................................................233 Figure 11: Mechanism of action of Herceptin..................................................................................236 Figure 12: A) Herceptin positive and negative BC patient split and B) Marketing opportunities for Herceptin in chemotherapy patients................................................................................................238 Figure 13: Herceptin has a comprehensive clinical trial programme to drive future sales growth..238 Figure 14: Expected US launch times for BC therapeutics .............................................................242 Figure 15: Avastin strong US launch...............................................................................................258 Figure 16: Mechanism of action of IGN101.....................................................................................265 Figure 17: Schematic of multidrug resistant inhibitors (MDRIs) blockade. .....................................268 Figure 18: Global oncology market - US$24 billion (2004) .............................................................280 Figure 19: Key players in the oncology market (2004)....................................................................281 Figure 20: Global BC market by region 2004 - US$6.0 billion ........................................................282 Figure 21: Global BC market by therapy class 2004 - US$6.0 billion .............................................283 Figure 22: Global BC market by region 2012E - US$8.9 billion......................................................284 Figure 23: Global BC market by therapy class 2012 - US$8.9 billion .............................................284 Figure 24: Market share of BC players by sales (2004A) ...............................................................285 Figure 25: Market share of BC players by sales (2012E) ...............................................................290

CANCER DRUG DISCOVERIES COLORECTAL CANCER CONTENTS


COLORECTAL CANCER CONTENTS

COLORECTAL CANCER (CRC)..................................................................................................303


BACKGROUND TO CRC .............................................................................................................304

What is CRC and how does it affect patients? .........................................................................304


Patient growth drivers ................................................................................................................308 The prevalence of people living with CRC will increase by 14% by 2012 ........................................308

Drug growth drivers ....................................................................................................................309

CURRENT TREATMENTS ...........................................................................................................310

CHEMOTHERAPY........................................................................................................................311 SWOT analysis of individual chemotherapy treatments....................................................................313

5-fluorouracil ..........................................................................................................................................313 Eloxatin (sanofi-aventis).........................................................................................................................314

Strengths .........................................................................................................................................315 Weaknesses....................................................................................................................................315 Opportunities ...................................................................................................................................316 Threats ............................................................................................................................................317 Sales forecasts................................................................................................................................317

Camptosar (Pfizer).................................................................................................................................318 Strengths .........................................................................................................................................318 Weaknesses....................................................................................................................................319 Opportunities ...................................................................................................................................319 Threats ............................................................................................................................................319 Sales forecasts................................................................................................................................320

Tomudex (AstraZeneca) ........................................................................................................................320 Strengths .........................................................................................................................................321 Weaknesses....................................................................................................................................321 Sales forecasts................................................................................................................................321

Xeloda (Roche) ......................................................................................................................................321 Mechanism of action .......................................................................................................................322 Strengths .........................................................................................................................................322 Weaknesses....................................................................................................................................322 Opportunities ...................................................................................................................................323 Threats ............................................................................................................................................323 Sales forecasts................................................................................................................................323

IMMUNOTHERAPY ......................................................................................................................324

COLORECTAL CANCER CONTENTS CANCER DRUG DISCOVERIES


SWOT analysis of individual immunotherapies ..................................................................................324 Rationale for targeting the epidermal growth factor pathway in colorectal cancer ........................324

Erbitux (ImClone Systems / Bristol-Myers Squibb)................................................................................326 Strengths .........................................................................................................................................326 Weaknesses ....................................................................................................................................328 Opportunities ...................................................................................................................................328 Threats ............................................................................................................................................329 Sales forecasts ................................................................................................................................329

Iressa (Astra Zeneca).............................................................................................................................330 Mechanism of action........................................................................................................................330 Strengths .........................................................................................................................................330 Weaknesses ....................................................................................................................................331 Opportunities ...................................................................................................................................331 Threats ............................................................................................................................................331 Sales forecasts ................................................................................................................................332

Avastin (Genentech) ..............................................................................................................................332 Strengths .........................................................................................................................................332 Weaknesses ....................................................................................................................................334 Opportunities ...................................................................................................................................334 Threats ............................................................................................................................................335 Sales forecasts ................................................................................................................................335

Sales forecast of CRC drugs .....................................................................................................337

RESEARCH & DEVELOPMENT OF CRC DRUGS .....................................................................341

Phase I-III drugs of interest........................................................................................................343 Antifolate .................................................................................................................................................347

Alimta (Eli Lilly) - Phase II ......................................................................................................................347 Strengths .........................................................................................................................................347 Weaknesses ....................................................................................................................................348 Opportunities ...................................................................................................................................348 Threats ............................................................................................................................................348 Sales forecasts ................................................................................................................................348

Novel therapies .......................................................................................................................................348 Targeting the epidermal growth factor pathway.....................................................................................348 Vatalanib (PTK/ZK, Schering AG / Novartis) - Phase III ........................................................................349

Strengths .........................................................................................................................................349 Weaknesses ....................................................................................................................................352 Opportunities ...................................................................................................................................353 Threats ............................................................................................................................................353 Filing and sales forecasts................................................................................................................353

Panitumumab (Amgen / Abgenix) - Phase II..........................................................................................354 Strengths .........................................................................................................................................355 Weaknesses ....................................................................................................................................355



Opportunities ...................................................................................................................................356 Threats ............................................................................................................................................356 Filing and sales forecasts................................................................................................................356

Alternative targeted approaches ..........................................................................................................357 Ispinesib (GlaxoSmithKline) - Phase II ..................................................................................................357

Strengths .........................................................................................................................................358 Weaknesses....................................................................................................................................358 Opportunities ...................................................................................................................................358 Threats ............................................................................................................................................359 Probability of success and sales forecasts .....................................................................................359

TNFerade (GenVec) - Phase II..............................................................................................................360 Strengths .........................................................................................................................................360 Weaknesses....................................................................................................................................360 Opportunities ...................................................................................................................................361 Threats ............................................................................................................................................362 Probability of success and sales forecasts .....................................................................................362

Velcade (Millennium Pharmaceuticals / Johnson & Johnson) - Phase III .............................................362 Scientific rationale ...........................................................................................................................362 Strengths .........................................................................................................................................362 Weaknesses....................................................................................................................................363 Opportunities ...................................................................................................................................363 Threats ............................................................................................................................................363 Probability of success and sales forecasts .....................................................................................363

Cotara (Peregrine Pharmaceuticals / Medipharm Biotech) - Phase III..................................................364 Scientific rationale ...........................................................................................................................364 Strengths .........................................................................................................................................364 Weaknesses....................................................................................................................................364 Opportunities ...................................................................................................................................365 Threats ............................................................................................................................................366 Probability of success and sales forecasts .....................................................................................366

Cancer vaccines .....................................................................................................................................366 TroVax (Oxford BioMedica) - Phase II...................................................................................................366

Strengths .........................................................................................................................................366 Weaknesses....................................................................................................................................367 Opportunities ...................................................................................................................................367 Threats ............................................................................................................................................367 Probability of success and sales forecasts .....................................................................................367

IGN101 (Aphton Corporation) - Phase II ...............................................................................................368 Strengths .........................................................................................................................................368 Weaknesses....................................................................................................................................369 Opportunities ...................................................................................................................................369 Threats ............................................................................................................................................369 Probability of success and sales forecasts .....................................................................................370

ALVAC-CEA/B7.1 (sanofi pasteur / Therion Biologics) - Phase II.........................................................370

COLORECTAL CANCER CONTENTS CANCER DRUG DISCOVERIES


Scientific rationale ...........................................................................................................................370 Strengths .........................................................................................................................................371 Weaknesses ....................................................................................................................................371 Opportunities ...................................................................................................................................371 Threats ............................................................................................................................................372 Sales forecasts ................................................................................................................................372

EP-2101 (Epimmune) - Phase II ............................................................................................................372 Strengths .........................................................................................................................................372 Weaknesses ....................................................................................................................................373 Opportunities ...................................................................................................................................373 Threats ............................................................................................................................................374 Probability of success and sales forecasts .....................................................................................374

Avicine (AVI BioPharma) Phase II ........................................................................................................374 Strengths .........................................................................................................................................374 Weaknesses ....................................................................................................................................375 Opportunities ...................................................................................................................................375 Threats ............................................................................................................................................375 Probability of success and sales forecasts .....................................................................................375

Theratope (Biomira) - Phase II...............................................................................................................376 Strengths .........................................................................................................................................376 Weaknesses ....................................................................................................................................376 Opportunities ...................................................................................................................................377 Threats ............................................................................................................................................377 Probability of success and sales forecasts .....................................................................................377

Chemotherapy drug enhancer ..............................................................................................................377 CoFactor (ADVENTRX Pharmaceuticals) - Phase II .............................................................................377

Strengths .........................................................................................................................................377 Weaknesses ....................................................................................................................................379 Opportunities ...................................................................................................................................379 Threats ............................................................................................................................................379 Probability of success and sales forecasts .....................................................................................379

New drug formulations...........................................................................................................................379 HyCAMP (Meditech Research) - Phase II .............................................................................................380

Technology ......................................................................................................................................380 Strengths .........................................................................................................................................381 Weaknesses ....................................................................................................................................381 Opportunities ...................................................................................................................................381 Threats ............................................................................................................................................382 Probability of success and sales forecasts .....................................................................................382

DAVANAT-1 (Pro-Pharmaceuticals ) - Phase II.....................................................................................382 Technology ......................................................................................................................................382 Strengths .........................................................................................................................................383 Weaknesses ....................................................................................................................................384 Opportunities ...................................................................................................................................384



Threats ............................................................................................................................................384 Probability of success and sales forecasts .....................................................................................385

LE-SN38 (NeoPharm ) - Phase I / II ......................................................................................................385 Strengths .........................................................................................................................................385 Weaknesses....................................................................................................................................386 Opportunities ...................................................................................................................................386 Threats ............................................................................................................................................386 Probability of success and sales forecasts .....................................................................................386

AP5346 (Access Pharmaceuticals) - Phase I ........................................................................................387 Strengths .........................................................................................................................................387 Weaknesses....................................................................................................................................388 Opportunities ...................................................................................................................................388 Threats ............................................................................................................................................388 Probability of success and sales forecasts .....................................................................................388

Alternative approaches to colorectal cancer treatment ..........................................................389 Cholesterol-lowering agents or statins .....................................................................................................389

Probability of success .....................................................................................................................390 Cyclooxygenase-2 or Cox-2 inhibitors ......................................................................................................391

Scientific rationale ...........................................................................................................................391 Probability of success .....................................................................................................................392




GLOBAL CRC MARKET..............................................................................................................396

Key companies in the CRC market............................................................................................399 Bristol-Myers Squibb..............................................................................................................................399 Pfizer ......................................................................................................................................................401 Roche.....................................................................................................................................................403 sanofi-aventis.........................................................................................................................................403

Leading CRC companies in 2012E .......................................................................................................405

BIBLIOGRAPHY...........................................................................................................................407

GLOSSARY ..................................................................................................................................410

APPENDIX 1 - US CRC DEMOGRAPHICS 2004-2012 ...............................................................413

APPENDIX 2 - EUROPEAN CRC DEMOGRAPHICS 2004-2012................................................414

APPENDIX 3 - JAPANESE CRC DEMOGRAPHICS 2004-2012.................................................415

COLORECTAL CANCER INDEX OF TABLES CANCER DRUG DISCOVERIES


COLORECTAL CANCER INDEX OF TABLES Table 1: Classification of CRC ........................................................................................................304 Table 2: Summary of global CRC patient population forecasts (2004A-2012E).............................311 Table 3: Treatment protocols for CRC ............................................................................................313 Table 4: Ongoing clinical trials with Eloxatin ...................................................................................316 Table 5: Xeloda clinical trial programme .........................................................................................323 Table 6: Ongoing clinical trials with Erbitux.....................................................................................327 Table 7: Ongoing trials with Iressa ..................................................................................................330 Table 8: Clinical development of Iressa ..........................................................................................332 Table 9: Avastin clinical development programme..........................................................................333 Table 10: Global sales for CRC 2004A-2012E (US$ millions)........................................................340 Table 11: Products in clinical development for the treatment of CRC ............................................341 Table 12: Global CRC sales of new products 2003A-2012E (US$ millions)...................................345 Table 13: HyACT-based cancer drugs in clinical development ......................................................380 Table 14: Cox cancer trials..............................................................................................................391 Table 15: CRC drugs discontinued during development.................................................................393 Table 16: BMS oncology franchise..................................................................................................400 Table 17: BMS oncology pipeline....................................................................................................400 Table 18: Pfizer oncology franchise ................................................................................................401 Table 19: Pfizer oncology pipeline ..................................................................................................402 Table 20: sanofi-aventis oncology franchise ...................................................................................404 Table 21: sanofi-aventis oncology pipeline .....................................................................................405

CANCER DRUG DISCOVERIES COLORECTAL CANCER INDEX OF CHARTS


COLORECTAL CANCER INDEX OF CHARTS Figure 1: Incidence of CRC in US and Western Europe.................................................................305 Figure 2: Estimated US cancer deaths (2004)................................................................................306 Figure 3: Incidence of CRC in men and women in the US .............................................................307 Figure 4: Overexpression of EGFr correlates with increased metastasis, decreased survival and a poor prognosis.................................................................................................................................325 Figure 5: Inhibition of EGFr prevents tumour growth and dissemination as well as inducing cell death (apoptosis).............................................................................................................................325 Figure 6: US Market share of Erbitux versus its competitors..........................................................329 Figure 7: Avastin strong US launch.................................................................................................336 Figure 8: Expected US launch times for CRC therapeutics............................................................339 Figure 9: Schematic of VEGF receptors .........................................................................................349 Figure 10: Design of the CONFIRM 1 trial ......................................................................................350 Figure 11: Results of the CONFIRM 1 trial - PFS...........................................................................351 Figure 12: Results of the CONFIRM 1 trial - LDH...........................................................................351 Figure 13: Results of the CONFIRM 1 trial - AEs ...........................................................................352 Figure 14: Results of the CONFIRM 1 trial - PFS in high HDL patients .........................................354 Figure 15: Mechanism of action of IGN101 ....................................................................................368 Figure 16: Avicine cancer vaccine clinical development programme .............................................376 Figure 17: Schematic of a Carbosome............................................................................................382 Figure 18: Pro-Pharmaceuticals product pipeline ...........................................................................384 Figure 19: Global oncology market - US$24 billion (2004) .............................................................394 Figure 20: Key players in the oncology market (2004) ...................................................................395 Figure 21: Global CRC market by region 2004 - US$3.2 billion .....................................................396 Figure 22: Global CRC market by therapy class 2004 - US$3.2 billion ..........................................397 Figure 23: Global CRC market by therapy class 2012 - US$5.6 billion ..........................................397 Figure 24: Global CRC market by region 2012 - US$5.6 billion .....................................................398 Figure 25: Market share of CRC players by sales (2004A) ............................................................399 Figure 26: Market share of CRC players by sales (2012E) ............................................................406

CANCER DRUG DISCOVERIES NON-SMALL CELL LUNG CANCER ... · CANCER DRUG DISCOVERIES NON-SMALL CELL...

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