標的療法市場動向

Overview

Introduction

The targeted therapies market is relatively new in comparison to the cytotoxic and anti-hormonal therapies markets, and will therefore continue to show double-figure growth across the seven major pharmaceutical markets to 2014. Despite products which have already established gold-standard status within specific tumor types, ample lucrative opportunities exist for pipeline candidates in the market.

Scope

• Overview of the current targeted therapies market, including profiles of key products and events impacting each during 2004-14
• Examination of the targeted therapies pipeline with in-depth clinical and commercial profiles of Phase III candidates, plus expert opinion
• Seven-market sales forecasts from 2004 to 2014 for branded targeted therapies and key pipeline candidates
• Detailed discussion of key strategic issues in the targeted therapies market, plus three commercial impact and lifecycle management case studies

Report Highlights

The targeted therapies market was worth $5.1 billion in 2004, and is set to grow at a CAGR of 13.7% to reach $13.7 billion by 2014. This is due to the novelty of this market, allowing for further increasing sales of current marketed products, with no immediate threat from patent expiries and generic competition.

This sustained growth will allow established products such as Genentech/Roches Rituxan and Novartiss Glivec to maintain their blockbuster status, while allowing newer products such as Genentech/Roches Herceptin, Avastin and Tarceva to break the $1 billion sales barrier within the forecast period.

The introduction of high-potential pipeline products will increase the total market value of targeted therapies to $19.2 billion by 2014. Those products developed to inhibit multiple pathways show the most promise, particularly Onyx Pharmaceuticals/Bayers sorafenib and Bristol-Myers Squibbs dasatinib, with forecast sales of over $800m by 2014.

Reasons to Purchase

• Understand market specific drivers and predict the future potential of key marketed and pipeline targeted therapies
• Assess the impact of product launches and identify the opportunities and risks for key products within the targeted therapies market
• Adopt knowledge to drive strategic planning for marketed products and optimize the market penetration of new entrants

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

• About the Oncology pharmaceutical analysis team
  • Richard Faint - Director of Oncology

CHAPTER 1 EXECUTIVE SUMMARY

• Scope of analysis
• Datamonitor insight into the targeted therapies market

CHAPTER 2 PIPELINE OVERVIEW

• Pipeline overview
• Pipeline by developmental phase & class of drug
  • Signal transduction inhibitors and angiogenesis inhibitorsconstitute over half the current targeted therapies pipeline
    • Signal transduction inhibitors & angiogenesisinhibitors dominate due to their wide applicability for use and provensuccess in the market to date
    • Setbacks suffered by Gentas Genasense may have deterredother developers of apoptosis stimulators
    • The specificity of monoclonal antibody target meanspatient potential is restricted, however, success of Rituxan may spurdevelopers on
    • The HDAC inhibitors & cell cycle regulators arerestricted in terms of potential molecular target, hence their minimalpresence in the pipeline
  • The current late-phase pipeline is relatively sparse dueto the novelty of this market
    • As time progresses, the late-phase pipeline will flourishas early-phase candidates move forward in development
• Pipeline by molecular target
  • Signal transduction inhibitors
    • The EGFR and multiple tyrosine kinases remain the focus ofdevelopment as targets for signal transduction inhibitors
  • Angiogenesis inhibitors
    • The VEGFR and multiple tyrosine kinases remain the focusof development as targets for angiogenesis inhibitors
  • Apoptosis stimulators
    • Due to a lack of information from developers, a populartarget for apoptosis is difficult to identify
  • HDAC inhibitors
  • Cell cycle regulators
    • Utility of CDK as a target comes from known mutation/overexpressionin some malignancies
  • Other monoclonal antibodies
    • The CD family of proteins allows for a highly specifictarget, with proven success via Rituxan
• Pipeline by indication
  • The big four tumor types, plus melanoma and RCC are themost popular indications for development
    • Constituting over half of all newly diagnosed cancercases, the big four tumor types offer significant commercial potential
    • Melanoma and RCC are well characterized in terms of tumorgrowth drivers, thus making them ideal indications for the development oftargeted therapies
  • Non-Hodgkins lymphoma dominates the pipeline within thehematological malignancies
    • Based on incidence rates, non-Hodgkins lymphoma is themost commercially attractive hematological indication for development
    • Pipeline compounds for leukemia are similar across thedifferent types, due to potential for horizontal expansion
• Pipeline by company
  • At least 138 companies are involved in the currenttargeted therapies pipeline
    • The majority of pipeline compounds are in early-phasetrials, hence two-thirds of companies involved are small biotechnologyfirms
  • Top three companies in terms of marketed and pipelineproducts are Genentech, AstraZeneca and Pfizer
    • Genentech
    • AstraZeneca
    • Pfizer
• Key metrics
• Datamonitor pipeline assessment summary

CHAPTER 3 PIPELINE DYNAMICS

• A diverse range of disease subtypes
• Genetic basis of cancer evolution
  • Tumorigenesis is the result of cooperative accumulatedmutations
• Existing pharmacotherapy approaches provide limitedtreatment benefit
  • Cytotoxic drugs lack specificity
  • Hormonal or endocrine therapy provides incremental benefitin selected tumors
  • Optimizing current treatment strategies is paramount
• The emergence of targeted treatment heralds a revolutionin cancer pharmacotherapy
• Dynamic cancer market offers significant commercialopportunity
  • Ongoing sales growth drives the market
  • Intensive R&D produces a rich developmental pipeline
  • Growing patient population and significant unmet needspropel innovation in the cancer market
    • Cancer epidemiology - an expanding patient base
    • Significant areas of unmet need persist
• Clinical and strategic threats to the commercialization ofcancer drugs
  • Progressively rising R&D costs threaten industryproductivity
    • High attrition rates can be mitigated by improvedstrategic decision-making
    • Lengthening drug approval process a consequence ofincreased regulatory demands
  • Pharmacoeconomic pressures drive payers to implementrestrictive pricing and reimbursement policies
  • Increased therapeutic and generic competition results inreduced periods of market exclusivity
  • Segmentation of market will require changes in clinicaltrial methodology

CHAPTER 4 MARKET DEFINITION & PIPELINE CLASSIFICATION

• Targeted therapies overview
  • The development of innovative targeted therapies
    • Current therapies adversely affect non-malignant cells
    • Innovative targeted therapies can address novel propertiesof tumor cells to selectively target them over normal cells
    • Key issue is the identification of targets unique tocancer cells
• Market definition
  • L1X3 - Antineoplastic monoclonal antibodies
  • L1X9 - All other antineoplastics
• Classification of pipeline products
  • Signal transduction inhibitors
    • A plethora of potential targets along the signalingcascade exist
    • Several signal transduction inhibitors have reached themarket, bringing with them their own sets of issues for consideration
  • Angiogenesis inhibitors
    • Angiogenesis as a normal biological process
    • Angiogenesis is known to be abberant in tumor cellproliferation
    • Angiogenesis inhibitors as viable antitumor agents cantarget a number of pathways
    • At present, only one angiogenesis inhibitor exists in themarket
  • Apoptosis stimulators
    • Cell death can be induced via a number of differentpathways
    • To date, only one apoptosis stimulator has reached themarket
  • Histone deacetylase inhibitors
    • Despite relative immaturity of development in this classof drugs, the potential to enhance current therapies exists
  • Cell cycle inhibitors
    • Despite ongoing R&D efforts, all current candidatesremain in the Phase II stage of development
• Pipeline comparator
• Current market situation

CHAPTER 5 MARKETED PRODUCTS FORECAST ANALYSIS

• Country-specific assumptions and effects
  • Effect of Medicare Modernization Act in the US
  • Biennial price cuts in Japan
  • National Institute of Clinical Excellence in the UK
• Product assumptions and effects
  • Signal transduction inhibitors
    • Erbitux (cetuximab)
    • Gleevec (imatinib)
    • Herceptin (trastuzumab)
    • Iressa (gefitinib)
    • Tarceva (erlotinib)
    • Targretin (bexarotene)
  • Angiogenesis inhibitors
    • Avastin (bevacizumab)
  • Apoptosis stimulators
    • Velcade (bortezomib)
  • Other monoclonal antibodies
    • Bexxar (tositumomab)
    • Campath (alemtuzumab)
    • Mylotarg (gemtuzumab)
    • MabThera/Rituxan (rituximab)
    • Zevalin (ibritumomab)
  • Others
    • Ontak (denileukin)
• Forecasts

CHAPTER 6 PIPELINE SIGNAL TRANSDUCTION INHIBITORS ANALYSIS& FORECASTS

• Pipeline overview
• Onyx Pharmaceuticals/Bayers sorafenib (BAY 43-9006)
  • Drug profile
    • Multi-targeted approach allows for clinical development ina wide range of tumors
  • Clinical trial data
    • Sorafenib in RCC moves into preregistration
    • Potential for monotherapy and combination therapy in HCC
    • Combination therapy provides opportunity in malignantmelanoma
    • Phase II clinical trials
    • Acceptable toxicity profile
  • Datamonitor comments
    • Despite sorafenibs convincing single-agent activity, fullpotential will lie in combination regimens
    • Potential first-to-market status and collaboration willensure sorafenib is the leading multi-kinase inhibitor
• Pfizers Sutent (sunitinib malate)
  • Drug profile
    • Development is ongoing in a variety of tumors due to wideapplicability of use of Sutent
  • Clinical trial data
    • Sutent shows significant activity among refractory GISTpatients with no alternative treatment options
    • Significant activity shown in second-line treatment ofRCC, though ongoing Phase III study is exploring first-line Sutentmonotherapy
    • Ongoing Phase II trial in breast cancer followingencouraging preliminary results
    • Activity shown in difficult to treat population withneuroendocrine tumors, although large-scale trials are yet to be initiated
    • Phase II clinical trials
    • Majority of Sutents toxicities are mild in nature
  • Datamonitor comments
    • Initial regulatory approval will come via GIST patients,although product expansion will need to occur to increase commercialpotential
    • Pfizers presence will be advantageous once Sutent gainsmarketing approval
• Abbott Laboratories Xinlay (atrasentan)
  • Drug profile
    • Xinlays target receptor plays a key role in cancer cellproliferation
  • Clinical trial data
    • ODAC decision indicates low probability of Xinlay beinggranted FDA approval for prostate cancer
    • Activity of Xinlay in NSCLC similar to standardchemotherapy
    • Other trials
  • Datamonitor comments
    • Clinical benefit among a patient population with fewtreatment options means Xinlay could fulfill a significant unmet need
    • Abbotts favorable position in the prostate cancer marketwill be invaluable in Xinlays market potential
• Abgenix/Amgens ABX-EGF (panitumumab)
  • Drug profile
    • Overexpression of EGFR makes an ideal target for ABX-EGFdevelopment
  • Clinical trial data
    • ABX-EGF shows promise as monotherapy or combinationtherapy across a range of treatment settings for colorectal cancer
    • Addition of ABX-EGF appears to enhance standardchemotherapy in NSCLC
    • Poor results as a single agent in RCC
    • Termination of development in prostate cancer
    • Main side effect is a potential indicator of ABX-EGFactivity
  • Datamonitor comments
    • Humanized nature of ABX-EGF holds some advantages overcompetitor EGFR inhibitors
    • Way forward for Amgen lies in ABX-EGF combination regimensand potential development of biomarker
    • Amgens presence will ensure success, althoughprofitability may increase by targeting earlier lines of therapy
• GlaxoSmithKlines lapatinib (GW-572016)
  • Drug profile
    • Lapatinib is unique among the EGFR inhibitors by targetingtwo receptor tyrosine kinases
  • Clinical trial data
    • HER-2 overexpression in breast cancer justifies validityof lapatinibs target
    • Limited single-agent activity indicates combinationregimens including lapatinib are the way forward in NSCLC
    • Limited activity has terminated development of lapatinibin colorectal cancer
    • Modest activity in urothelial tumors, although unclearwhether GlaxoSmithKline intends to pursue this indication
    • Infrequent incidence of Grade 3 or higher toxicity
  • Datamonitor comments
    • Initial approval in niche breast cancer indication willexpedite subsequent approvals, with potential blockbuster status forlapatinib
    • GlaxoSmithKline needs to account for deficiency inoncology market experience to take full advantage of lapatinibs potential
• Schering-Ploughs Sarasar (lonafarnib)
  • Drug profile
    • Previously wide range of developmental indications forSarasar has been reduced to just two
  • Clinical trial data
    • Main focus of Sarasar development in MDS, where greatestantitumor activity is shown
    • Lack of efficacy has led to termination of pivotal PhaseIII trial in NSCLC
    • Lack of clinical data makes it difficult to judgeSarasars potential in breast cancer
    • Benefit shown in advanced head and neck cancer, althoughno further trials have been announced
    • Limited activity as a single agent, although Sarasar mayshow potential in combination therapy in pancreatic cancer
    • Despite encouraging Phase II results in urothelial tractcarcinoma, no further clinical trials are planned
    • Lack of single-agent activity in colorectal cancer hashalted development in this indication
    • Mild toxicity in the majority of patients, although Grade3 events do occur
  • Datamonitor comments
    • The FDAs recent rejection of Johnson & JohnsonsZarnestra may reduce the time between launches of the two farnesyltransferase inhibitors
    • Presence in oncology market will aid commercialization ofSarasar
• Wyeths temsirolimus (CCI-779)
  • Drug profile
    • Temsirolimus inhibits a key pathway in tumor cellproliferation
  • Clinical trial data
    • Encouraging response rates seen for temsirolimus incombination with standard interferon-alfa for RCC in Phase I trials arebeing further investigated
    • Substantial antitumor activity in Phase II trials inmantle cell lymphoma led to initiation of a Phase III trial in January2005
    • Temsirolimus shows activity as a single agent and incombination with hormonal therapy in breast cancer
    • Temsirolimus shows some activity in SCLC, although Wyethhas not stated its intention to pursue this indication
    • Temsirolimus does not show activity as a single agent inmelanoma
    • Despite encouraging results, Wyeth is not pursuingglioblastome multiforme as a potential indication for temsirolimus
    • Mild toxicity means temsirolimus is well tolerated
  • Datamonitor comments
    • Lucrative opportunites exist for temsirolimus, althoughbroad commercialization would be expedited via an approval in a nicheindication
    • Prior commercialization of Mylotarg has given Wyeth theexperience to launch temsirolimus successfully
• AstraZenecas Zactima (ZD-6474)
  • Drug profile
    • Zactimas ability to inhibit both angiogenesis and signaltransduction should in theory result in greater efficacy in certainpatient subsets
  • Clinical trial data
    • Phase III trials investigating Zactima in NSCLC areplanned for second half of 2005
    • Phase II trial in multiple myeloma failed to meet primaryendpoint
    • Other trials
  • Datamonitor comments
    • Zactimas survival benefit in NSCLC needs to be convincingin order to compete with Tarceva
    • AstraZenecas strength in the oncology market will be keyin Zactimas success
• Janssen/Johnson & Johnsons Zarnestra (tipifarnib)
  • Drug profile
    • Previously wide range of developmental indications forZarnestra have been reduced to just one
  • Clinical trial data
    • Following rejection of an NDA, the FDA requires Phase IIIdata for Zarnestra in AML before regulatory approval can be considered
    • Zarnestra shows activity in MDS, although further study isnot planned in short-term future
    • Negative Phase III trial results caused termination ofdevelopment in pancreatic cancer
    • Negative Phase III trial results caused termination ofdevelopment in colorectal cancer
    • Zarnestra development in breast cancer remains in Phase IItrials
    • Minimal activity in prostate cancer has terminateddevelopment in this indication
    • Lack of activity in SCLC caused termination of Phase IItrial
    • Phase I trial is ongoing for Zarnestra in combination withchemotherapy in advanced NSCLC
    • Despite modest activity in brain cancer, follow-up trialshave not been initiated
    • Mild toxicity is particularly significant sinceZarnestras main indication is for elderly AML patients where quality oflife is a major issue
  • Datamonitor comments
    • FDA rejection has caused Zarnestra to lose its lead
    • Focus on gene expression profiling may lead tofragmentation of the market
    • Johnson & Johnsons experience will be invaluable toZarnestra
    • Zarnestras niche indication may dilute effects of itsprobable first-to-market status loss
• Bristol-Myers Squibbs dasatinib (BMS-354825)
  • Drug profile
    • Dasatinib shows potential to overcome Gleevec resistance
  • Clinical trial data
    • Dasatinib overcomes Gleevec resistance in CML patients
    • Phase I study of dasatinib in solid tumors is ongoing
  • Datamonitor comments
    • Despite convincing clinical benefit, dasatinib alreadyfaces potential competition from Novartiss AMN-107
    • Bristol-Myers Squibbs extensive oncology experience willaid commercializatioan of dasatinib
• Novartiss AMN-107
  • Drug profile
    • AMN-107 shows potential for greater efficacy than Gleevec
  • Clinical trial data
    • AMN-107 confers significant activity in Gleevec-resistantCML
  • Datamonitor comments
    • AMN-107 in a race with Bristol-Myers Squibbs dasatinib toreach the market first
    • An opportunity for Novartis to consolidate and expand itsleading role in the CML therapy market
• Kosan Biosciences 17-AAG
  • Drug profile
    • Potential to disrupt a host of relevant oncology targetsmeans 17-AAG shows a wide range of applicability
  • Clinical trial data
    • 17-AAG as a single agent induced disease stabilization inmelanoma patients
    • 17-AAG with docetaxel resulted in minor tumor responses
    • 17-AAG with gemcitabine and cisplatin resulted in twopartial responses
    • Some evidence of 17-AAG activity in multiple myeloma
    • Phase II trials
  • Datamonitor comments
    • Although 17-AAGs formulation may provide setbacks,commercial potential can be increased by developing biomarkers to judgeresponse
    • Kosan Biosciences should recruit the experience andresources of a key oncology player
• Forecasts
• Datamonitor drug assessment summary

CHAPTER 7 PIPELINE ANGIOGENESIS INHIBITORS ANALYSIS &FORECASTS

• Pipeline overview
• National Cancer Institutes CAI (L-651582,carboxyamidotriazole)
  • Drug profile
    • Clinical trials completed in a range of tumor types,although further development is unclear
  • Clinical trial data
    • Phase III trial failed to demonstrate any benefit of CAIover placebo in NSCLC
    • Limited evidence for future development of CAI in RCC
    • Some activity in ovarian cancer, although furtherdevelopment is unclear
  • Datamonitor comments
    • CAI left virtually redundant by Avastin and otherlate-stage pipeline angiogenesis inhibitors with superior clinicalprofiles
    • Success of CAI depends solely on involvement of apharmaceutical company, which is unlikely to occur
• Aterna Zentariss Neovastat (AE-941)
  • Drug profile
    • Development of Neovastat scaled down to focus solely onNSCLC
  • Clinical trial data
    • Final results from Phase III trial in NSCLC expected in2006
    • Termination of Neovastat development in RCC followingfailure of Phase III to meet its primary endpoints
    • Other indications
  • Datamonitor comments
    • If ongoing Phase III trial does not meet its primaryendpoints, it could be the end for development of Neovastat
    • Aterna Zentaris should secure a US marketing partner inorder to increase commercial potential of Neovastat
• Novartis/Schering AGs PTK-787 (vatalinib)
  • Drug profile
    • By targeting all known VEGFR tyrosine kinases, PTK-787should show activity across a range of tumor types
  • Clinical trial data
    • Anticipated regulatory filing for PTK-787 in colorectalcancer delayed to 2007 following disappointing CONFIRM-1 interim results
    • Recent initiation of the Phase II GOAL Study in NSCLC
    • Phase II trial is ongoing for PTK-787 in glioblastomamultiforme
    • Development in other tumors remains in early phases
    • Majority of reported toxicities among 1,000 patients havebeen mild to moderate in nature
  • Datamonitor comments
    • PTK-787s distinct advantages could recoup any negativerepurcussions from the CONFIRM-1 interim results
    • Schering AG and particularly Novartiss prior oncologyexperience will be invaluable to PTK-787
• Pfizers AG-13736
  • Drug profile
  • Clinical trial data
    • AG-13736 shows substantial antitumor activity incytokine-refractory metastatic RCC
    • AG-13736 does not confer significant activity as a singleagent in AML and MDS
    • Demonstration of AG-13736 activity in Phase I study insolid tumors forms the basis of ongoing Phase II trials
  • Datamonitor comments
    • With a strategic development plan, Pfizer may be able toovercome Avastins leading position
    • Pfizers experience will be advantageous in thedevelopment of AG-13736
• Forecasts
• Datamonitor drug assessment summary

CHAPTER 8 PIPELINE APOPTOSIS STIMULATORS ANALYSIS &FORECASTS

• Pipeline overview
• Gentas Genasense (oblimersen)
  • Drug profile
    • Despite termination of Gentas agreement withSanofi-Aventis, Genasense remains in development for a multitude ofindications
  • Clinical trial data
    • Benefits of Genasense in CLL may not be enough to offsetthe addition of significant toxicity
    • Long-term survival results of Genasense in malignantmelanoma are of significance
    • Disappointing Phase III trial results in multiple myelomameans status of further development is unclear
    • Early-phase benefits of Genasense in AML requireconfirmation in Phase III clinical trial
    • Lack of clinical data in NSCLC makes it difficult to judgeGenasenses potential
    • Encouraging Phase II results in prostate cancer, thoughPhase III trials have yet to be initiated
    • Ongoing Phase II trial in SCLC will determine if patientbenefit counters additional toxicity
    • Promise shown in combination with rituximab in NHL, butrandomized trials have yet to be initiated
    • Genasense did not enhance activity of standardinterferon-alfa in RCC
    • Other trials
  • Datamonitor comments
    • Wide range of developmental indications for Genasenseprovides Genta with a significant commercial opportunity
    • Termination of agreement with Sanofi-Aventis is a majorsetback for Genta
• Teliks Telcyta (TLK286)
  • Drug profile
    • Synergy of Telcyta with standard cytotoxics may indicate awide ranging applicability for use
  • Clinical trial data
    • Convincing Phase II results have initiated two large-scalePhase III trials in ovarian cancer
    • Benefit of Telcyta in combination with standardchemotherapy shown in NSCLC
    • Telcyta shows some activity as a single agent in breastcancer, although final Phase II results have yet to be published
    • Uncertain status of Telcyta in colorectal cancer
  • Datamonitor comments
    • Telik should seek initial approval of Telcyta in ovariancancer, which should expedite subsequent submissions
    • In light of the competition Tarceva will provide forTelcyta, Telik would be prudent in seeking a commercialization partner
• Xenovas TransMID (XR-311)
  • Drug profile
    • TransMIDs target is highly relevant in brain cancer
  • Clinical trial data
    • Encouraging Phase II results, active clinical trialprogram and fast-track designation will drive development of TransMID
  • Datamonitor comments
    • Cumbersome infusion schedule and administration maydetract from TransMIDs broad clinical benefit
    • Although Xenova has secured several marketingpartnerships, a glaring omission is one in the lucrative US market
• Forecasts
• Datamonitor drug assessment summary

CHAPTER 9 PIPELINE HISTONE DEACETYLASE INHIBITORS ANALYSIS& FORECASTS

• Pipeline overview
• Gloucester Pharmaceuticals FK-228 (depsipeptide)
  • Drug profile
    • Broad range of HDAC inhibition should theoreticallyprovide increased efficacy
  • Clinical trial data
    • Encouraging results in cutaneous T-cell lymphoma requirereplication in ongoing Phase III clinical trial
    • A lack of clinical data exists, despite FK-228s Phase IIstatus in prostate cancer and RCC
  • Datamonitor comments
    • FK-228 likely to become the first HDAC inhibitor to reachthe market
    • Commercial success of FK-228 will rely on GloucesterPharmaceuticals collaborating with large pharma
• Forecasts
• Datamonitor drug assessment summary

CHAPTER 10 OTHER PIPELINE MONOCLONAL ANTIBODIES ANALYSIS& FORECASTS

• Pipeline overview
• Millennium Pharmaceuticals/BZL Biologicss MLN-2704
  • Drug profile
    • MLN-2704 has been developed specifically for prostatecancer
  • Clinical trial data
    • High doses of MLN-2704 resulted in tumor response andreduction in PSA levels in progressive, metastatic HRPC patients
  • Datamonitor comments
    • Significant opportunity lies in the prostate cancermarket, although future expansion could occur within other tumor types
    • Experience gained in commercialization of Velcade will beinvaluable in the development of MLN-2704
• Forecasts
• Datamonitor drug assessment summary

CHAPTER 11 COMMERCIAL IMPACT & LIFECYCLE MANAGEMENT:CASE STUDIES

• Introduction
• Case study 1
  • Iressa and Tarceva: why the difference?
    • How have two nearly identical drugs realized such varyinglevels of success in the NSCLC market?
    • Iressas Phase II survival benefit was sufficient togarner FDA approval
    • Concerns over Iressas potential toxicity restricted itsuse in Japan
    • FDA approval of Tarceva was based on a Phase III trialthat demonstrated a two-month survival benefit in the third-line NSCLCsetting
    • Phase III ISEL trial comparing Iressa with placebo inadvanced NSCLC failed to show survival benefit
    • Negative repercussions of the Iressas failed Phase IIItrial
    • Tarcevas potential is currently limited by Alimta in thesecond-line setting, although line extensions will increase uptake andsales
    • What if Iressa had not failed?
    • Could Iressa pose a threat to Tarceva?
    • Future opportunities are plentiful for Tarceva and Iressa
• Case study 2
  • Strategies for success: Genentech
    • A leading oncology player with winning strategies
    • Strengths and weaknesses of a collaborative partnership
    • The prime example
  • Strategies for success: Novartis
    • An entirely new strategy for the pharmaceutical industry
    • Early-phase development was slow...
    • ...although subsequent approval and launch was remarkablyquick
    • Approval for a second indication granted only nine monthsafter Gleevecs initial approval
    • Opportunities for continued growth exist...
    • ...although some drawbacks and threats have arisen
    • The rewards of this strategy are very attractive todevelopers
• Case study 3
  • The pharmacoeconomic challenges associated with targetedtherapies
    • Unique pharmacoeconomic challenges will arise as targetedtherapies are included in standard chemotherapy regimens
    • The cost of standard chemotherapy for cancer
    • The inclusion of targeted therapies into standardtreatment regimens
    • The impact of monoclonal antibody targeted therapies
    • The impact of small molecule targeted therapies
    • The problem of adding targeted therapies to standardchemotherapy regimens
    • Further effects of pharmacoeconomic issues
    • Communicating the value of targeted therapies

APPENDIX A - MARKET DATA & MAJOR BRAND KEY FACTS

• L1X3 (antineoplastic monoclonal antibodies) class marketdata
• L1X9 (all other neoplastics) class market data
• Sales data and forecasts
• PowerPoint Executive Presentation

• APPENDIX B - SALES FORECASTS
  • US forecasts
  • Japan forecasts
  • France forecasts
  • Germany forecasts
  • Italy forecasts
  • Spain forecasts
  • UK forecasts
  • EU5 forecasts
  • Global forecasts
• APPENDIX C
  • List of tables
  • List of figures
  • Methodology
    • Datamonitor forecast methodology
      • Forecasts for marketed drugs
      • Forecasts for pipeline drugs
    • Datamonitor drug assessment methodology
  • List of abbreviations
  • Contributing experts
    • US opinion leader 1
    • US opinion leader 2
  • Bibliography
  • About Datamonitor
    • About Datamonitor Healthcare
    • About the Oncology analysis team
• Disclaimer

List of Tables

• Table 1: Targeted therapies in preregistration, 2005
• Table 2: Targeted therapies in Phase III development,2005
• Table 3: Pipeline targeted therapies by developmentphase & class of drug, 2005
• Table 4: Pipeline signal transduction inhibitors bytarget, 2005
• Table 5: Pipeline angiogenesis inhibitors in developmentby target, 2005
• Table 6: Pipeline apoptosis stimulators in developmentby target, 2005
• Table 7: Pipeline cell cycle regulators in developmentby target, 2005
• Table 8: Pipeline monoclonal antibodies in developmentby target, 2005
• Table 9: Pipeline targeted therapies by indication, 2005
• Table 10: Genentechs marketed oncology portfolio, 2005
• Table 11: Genentechs pipeline oncology portfolio, 2005
• Table 12: AstraZenecas marketed oncology portfolio,2005
• Table 13: AstraZenecas pipeline oncology portfolio,2005
• Table 14: Pfizers marketed oncology portfolio, 2005
• Table 15: Pfizers pipeline oncology portfolio, 2005
• Table 16: Late-phase pipeline targeted therapies salesforecasts ($m), 2005-14
• Table 17: Datamonitor drug assessment summary
• Table 18: Common mutations involved in tumor development
• Table 19: Forecast incidence of cancer across the sevenmajor markets, 2005-13
• Table 20: Examples of naturally occurring angiogenesisstimulators
• Table 21: Current marketed products in the targetedtherapies market, (1 of 2)
• Table 22: Current marketed products in the targetedtherapies market, (2 of 2)
• Table 23: Targeted therapies sales in the seven majormarkets, 2003-04
• Table 24: Late-phase pipeline signal transductioninhibitors in development, 2005 (1 of 2)
• Table 25: Late-phase pipeline signal transductioninhibitors in development, 2005 (2 of 2)
• Table 26: Phase II pipeline signal transductioninhibitors in development, 2005 (1 of 2)
• Table 27: Phase II pipeline signal transductioninhibitors in development, 2005 (2 of 2)
• Table 28: Phase I pipeline signal transductioninhibitors in development, 2005
• Table 29: Ongoing clinical trials involving sorafenib
• Table 30: Ongoing clinical trials involving Sutent
• Table 31: Ongoing clinical trials involving Xinlay
• Table 32: Ongoing clinical trials involving ABX-EGF
• Table 33: Ongoing clinical trials involving lapatinib
• Table 34: Ongoing clinical trials involving Sarasar
• Table 35: Ongoing clinical trials involving temsirolimus
• Table 36: Ongoing clinical trials involving Zactima
• Table 37: Ongoing clinical trials involving Zarnestra
• Table 38: Ongoing clinical trials involving dasatinib
• Table 39: Ongoing clinical trials involving AMN-107
• Table 40: Ongoing clinical trials involving 17-AAG
• Table 41: Xinlay & Sutent forecasting assumptions
• Table 42: Sorafenib & ABX-EGF forecastingassumptions
• Table 43: Lapatinib & Sarasar forecastingassumptions
• Table 44: Temsirolimus & Zactima forecastingassumptions
• Table 45: Zarnestra, dasatinib & AMN-107 forecastingassumptions
• Table 46: Signal transduction inhibitors sales forecasts($m), 2005-14
• Table 47: Research/clinical and commercialattractiveness of pipeline signal transduction inhibitors (1 of 3)
• Table 48: Research/clinical and commercialattractiveness of pipeline signal transduction inhibitors (2 of 3)
• Table 49: Research/clinical and commercialattractiveness of pipeline signal transduction inhibitors (3 of 3)
• Table 50: Late-phase pipeline angiogenesis inhibitors indevelopment, 2005
• Table 51: Phase II pipeline angiogenesis inhibitors indevelopment, 2005
• Table 52: Phase I pipeline angiogenesis inhibitors indevelopment, 2005
• Table 53: Ongoing clinical trials involving Neovastat
• Table 54: Ongoing clinical trials involving PTK-787
• Table 55: Ongoing clinical trials involving AG-13736
• Table 56: PTK-787, Neovastat & AG-13736 forecastingassumptions
• Table 57: Angiogenesis inhibitors sales forecasts ($m),2005-14
• Table 58: Research/clinical and commercialattractiveness of pipeline angiogenesis inhibitors
• Table 59: Late-phase pipeline apoptosis stimulators indevelopment, 2005
• Table 60: Phase II pipeline apoptosis stimulators indevelopment, 2005 (1 of 2)
• Table 61: Phase II pipeline apoptosis stimulators indevelopment, 2005 (2 of 2)
• Table 62: Phase I pipeline apoptosis stimulators indevelopment, 2005
• Table 63: Ongoing clinical trials involving Genasense
• Table 64: Ongoing clinical trials involving Telcyta
• Table 65: Ongoing clinical trials involving TransMID
• Table 66: Genasense forecasting assumptions
• Table 67: Telcyta & TransMID forecasting assumptions
• Table 68: Apoptosis stimulators sales forecasts ($m),2005-14
• Table 69: Research/clinical and commercialattractiveness of pipeline apoptosis stimulators
• Table 70: Pipeline histone deacetylase inhibitors indevelopment, 2005
• Table 71: Ongoing clinical trials involving FK-228
• Table 72: FK-228 forecasting assumptions
• Table 73: FK-228 sales forecasts ($m), 2005-14
• Table 74: Research/clinical and commercialattractiveness of FK-228
• Table 75: Phase II/III pipeline monoclonal antibodies indevelopment, 2005 (1 of 2)
• Table 76: Phase II/III pipeline monoclonal antibodies indevelopment, 2005 (2 of 2)
• Table 77: Phase I pipeline monoclonal antibodies indevelopment, 2005
• Table 78: Ongoing clinical trials involving MLN-2704
• Table 79: MLN-2704 forecasting assumptions
• Table 80: MLN-2704 sales forecasts ($m), 2005-14
• Table 81: Research/clinical and commercialattractiveness of MLN-2704
• Table 82: Key Iressa & Tarceva events in the NSCLCmarket
• Table 83: Rituxan: key facts
• Table 84: Herceptin: key facts
• Table 85: Campath: key facts
• Table 86: Mylotarg: key facts
• Table 87: Bexxar: key facts
• Table 88: Avastin: key facts
• Table 89: Erbitux: key facts
• Table 90: Zevalin: key facts
• Table 91: Gleevec: key facts
• Table 92: Targretin: key facts
• Table 93: Iressa: key facts
• Table 94: Velcade: key facts
• Table 95: Tarceva: key facts
• Table 96: Ontak: key facts
• Table 97: Forecasts for antineoplastic monoclonalantibodies in the US, 2004-14
• Table 98: Forecasts for all other antineoplastics in theUS, 2004-14
• Table 99: Forecasts for marketed targeted therapies inJapan, 2004-14
• Table 100: Forecasts for marketed targeted therapies inFrance, 2004-14
• Table 101: Forecasts for marketed targeted therapies inGermany, 2004-14
• Table 102: Forecasts for marketed targeted therapies inItaly, 2004-14
• Table 103: Forecasts for marketed targeted therapies inSpain, 2004-14
• Table 104: Forecasts for marketed targeted therapies inthe UK, 2004-14
• Table 105: Forecasts for marketed targeted therapies inthe EU5, 2004-14
• Table 106: Global forecasts for antineoplasticmonoclonal antibodies, 2004-14
• Table 107: Global forecasts for all otherantineoplastics, 2004-14
• Table 108: Datamonitor drug assessment parameters
• Table 109: Abbreviations used in Pipeline/CommercialInsight: Innovative Targeted Therapies (1 of 2)
• Table 110: Abbreviations used in Pipeline/CommercialInsight: Innovative Targeted Therapies (2 of 2)

List of Figures

• Figure 1: Signal transduction inhibitors andangiogenesis inhibitors form the bulk of the 2005 targeted therapiespipeline
• Figure 2: A plethora of current early-phase agents willcome to light in the short-term future
• Figure 3: Targeting multiple tyrosine kinases appears tobe the current trend in R&D
• Figure 4: Targeting the primary VEGF receptor appearsthe most popular development strategy
• Figure 5: The majority of developmental agents affectunspecified apoptosis targets
• Figure 6: CDK appears to be the primary developmentaltarget for the cell cycle regulators
• Figure 7: The CD family of proteins appears mostfavorable for development
• Figure 8: Big four tumor types, plus melanoma and RCC,remain popular indications
• Figure 9: Hematological indications with the highestincidence dominate the developmental pipeline
• Figure 10: The majority of pipeline compounds are inearly-phase trials, therefore a high level of fragmentation exists
• Figure 11: Pipeline signal transduction inhibitors salesforecasts, 2005-14
• Figure 12: Pipeline angiogenesis inhibitors salesforecasts, 2005-14
• Figure 13: Pipeline apoptosis stimulators salesforecasts, 2005-14
• Figure 14: Pipeline HDAC inhibitors sales forecasts,2005-14
• Figure 15: Pipeline monoclonal antibodies salesforecasts, 2005-14
• Figure 16: Datamonitor drug assessment summary forpipeline signal transduction inhibitors
• Figure 17: Datamonitor drug assessment summary forpipeline angiogenesis inhibitors
• Figure 18: Datamonitor drug assessment summary forpipeline apoptosis stimulators
• Figure 19: Datamonitor drug assessment summary forpipeline HDAC inhibitors
• Figure 20: Datamonitor drug assessment summary forpipeline monoclonal antibodies
• Figure 21: Global oncology sales, 2002-09
• Figure 22: Oncology pipeline, 2003
• Figure 23: Forecast incidence of cancer across the sevenmajor markets, 2005-13
• Figure 24: Increasing combined incidence for breast,lung, prostate and colorectal cancer with increasing age, 2003
• Figure 25: Incidence increases, while the rate of cureand death reduces disease prevalence
• Figure 26: Point prevalence for colorectal and lungcancer differs markedly despite similar rates of incidence
• Figure 27: Unmet needs in cancer
• Figure 28: The process of tumor angiogenesis
• Figure 29: The multiple tyrosine kinase inhibitors willachieve the greatest commercial success
• Figure 30: The multiple tyrosine kinase inhibitorsappear most attractive in terms of research/clinical and commercialaspects
• Figure 31: PTK-787 is currently the front runner of theangiogenesis inhibitors due to the high patient potential of itsindication
• Figure 32: Candidates with the backing of key oncologyplayers appear most attractive among the pipeline angiogenesis inhibitors
• Figure 33: Genasense is the clear leader due to its widerange of developmental indications
• Figure 34: Route of administration may work against thepipeline apoptosis stimulators
• Figure 35: FK-228s sales are currently limited by itstarget indication
• Figure 36: A lack of clinical data and commercialexperience currently limit FK-228s attractiveness
• Figure 37: MLN-2704s commercial potential will increaseonce indications outside of prostate cancer are explored
• Figure 38: Attractiveness of MLN-2704 will increase oncedevelopment outside of prostate cancer is initiated
• Figure 39: Example of Datamonitor drug assessmentscorecard
• Figure 40: Example of Datamonitor drug assessment graph