Report: Pipeline/Commercial Insight: Molecular Targeted Cancer Therapies - More drugs on the market, more targets in the pipeline TOC

ABOUT DATAMONITOR HEALTHCARE
- About the Oncology pharmaceutical analysis team
  - Nish Saini - 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 and class of drug
  - The cell cycle and apoptosis targeted agents make up the largest number of MTTs in the pipeline
  - Segmentation of drugs by developmental phase reflects attrition rate of drug development in the oncology market
    - Targeted therapy remains a promising anticancer drug development strategy
    - Developmental agents by phase for each class
- Pipeline by indication
  - MTTs are being investigated in 29 different cancers
    - The ' big four' tumor types are the most popular indications for development
- Pipeline by mode of action
  - Pipeline MTTs are being directed against a huge variety and combination of molecular targets
  - The VEGF/VEGFR family remains the focus of development for MTTs
- Pipeline by company
  - There are over 150 different companies developing targeted therapies
  - Top three companies in terms of number of pipeline MTT products are Pfizer, Novartis and GlaxoSmithKline
    - Pfizer
    - Novartis
    - GlaxoSmithKline
- 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 co-operative accumulated mutations
- Existing pharmacotherapy approaches provide limited treatment benefit
  - Cytotoxic drugs lack specificity
  - Hormonal or endocrine therapy provides incremental benefit in selected tumors
  - Optimizing current treatment strategies is paramount
- The emergence of targeted treatment heralds a revolution in cancer pharmacotherapy
- Dynamic cancer market offers significant commercial opportunity
  - Ongoing sales growth drives the market
  - Intensive R&D produces a rich developmental pipeline
  - Growing patient population and significant unmet needs propel innovation in the cancer market
    - Cancer epidemiology - an expanding patient base
    - Significant areas of unmet need persist
- Clinical and strategic threats to the commercialization of cancer drugs
  - Progressively rising R&D costs threaten industry productivity
    - High attrition rates can be mitigated by improved strategic decision-making
    - Lengthening drug approval process - a consequence of increased regulatory demands
  - Pharmacoeconomic pressures drive payers to implement restrictive pricing and reimbursement policies
  - Therapeutic and generic competition reduces periods of market exclusivity
  - Segmentation of market will require changes in clinical trial methodology
CHAPTER 4 MARKET DEFINITION & PIPELINE CLASSIFICATION
- Targeted therapies overview
  - The development of molecular targeted therapies
    - Current therapies are less cancer cell-specific
    - The strategy is to target the specific survival factors of a tumor
    - Key issue is the identification of targets unique to cancer cells
- Market definition
  - L1X3 - Antineoplastic monoclonal antibodies
  - L1X9 - All other antineoplastics
- Classification of pipeline products
  - Angiogenesis inhibitors
    - Angiogenesis as a normal biological process
    - Angiogenesis is known to be abberant in tumor cell proliferation
    - Angiogenesis inhibitors as viable antitumor agents can target a number of pathways
    - At present, only one angiogenesis inhibitor exists in the market
  - Single-target signal transduction inhibitors
    - A plethora of potential targets exist along the signaling cascade
    - Several signal transduction inhibitors have reached the market, bringing with them their own sets of issues for consideration
  - Multi-targeted inhibitors
    - Multi-targeted inhibitors have certain advantages over single targeted agents
    - Approval of three multi-targeted inhibitors
  - Cell cycle and apoptosis targeted inhibitors
    - Only one cell cycle inhibitor has entered Phase III
    - Cell death can be induced via a number of different pathways
    - To date, only one apoptosis stimulator has reached the market
  - Epigenetic modulators
    - Despite relative immaturity of development in this class of drugs, the potential to enhance current therapies exists
  - Immunomodulatory and immunoconjugated therapeutics
    - Antibody-based technologies are an effective anticancer approach
- 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
  - Generic erosion assumptions
- Product assumptions and effects
  - Angiogenesis inhibitors
    - Genentech/Roche' s Avastin (bevacizumab)
  - Single-target signal transduction inhibitors
    - ImClone/Bristol-Myers Squibb/Merck KGaA' s Erbitux (cetuximab)
    - Novartis' s Gleevec/Glivec (imatinib)
    - Genentech/Roche' s Herceptin (trastuzumab)
    - AstraZeneca' s Iressa (gefitinib)
    - OSI Pharmaceuticals/Genentech/Roche' s Tarceva (erlotinib)
    - Eisai' s Targretin (bexarotene)
  - Multi-targeted inhibitors
    - Onyx Pharmaceuticals/Bayer AG' s Nexavar (sorafenib)
    - Bristol-Myers Squibb' s Sprycel (dasatinib)
    - Pfizer' s Sutent (sunitinib)
  - Cell cycle and apoptosis targeted agents
    - Ortho Biotech/Millennium Pharmaceuticals' Velcade (bortezomib)
  - Immunomodulatory and immunoconjugated therapeutics
    - GlakoSmithKline' s Bexxar (tositumomab)
    - Schering AG/Berlex' s Campath (MabCampath; alemtuzumab)
    - Wyeth' s Mylotarg (gemtuzumab)
    - Biogen IDEC/Genentech/Roche' s Rituxan/MabThera (rituximab)
    - Biogen Idec/Schering AG' s Zevalin (ibritumomab)
    - Eisai' s Ontak (Onzar; denileukin)
- Forecasts
CHAPTER 6 PIPELINE ANGIOGENESIS INHIBITORS ANALYSIS & FORECASTS
- Pipeline overview
- AstraZeneca' s AZD2171
  - Drug Profile
  - Clinical Trial Data
    - AZD2171 as a monotherapeutic agent
    - AZD2171 in combination with chemotherapy appears to be a promising approach
    - AZD2171 has potential in NSCLC in combination with standard chemotherapy regimens and with Iressa
  - Datamonitor Comments
    - As a potentially more potent inhibitor of angiogenesis, and given its formulation, AZD2171' s future may be very promising
    - AstraZeneca' s strength in the oncology market will be key in AZD2171' s success
- GlaxoSmithKline' s Pazopanib (GW 786034)
  - Drug Profile
  - Clinical Trial Data
    - Pazopanib as a possible second-line monotherapy treatment for metastatic RCC
    - Co-administration with Tykerb may alter the pharmacokinetics of pazopanib
    - Other Indications
  - Datamonitor Comments
    - Initial approval in RCC will force pazopanib to compete against the already approved Sutent and Nexavar
    - Tykerb may well enhance the success of pazopanib but at what price?
- Novartis/Schering AG' s Vatalanib (PTK-787)
  - Drug Profile
  - Clinical Trial Data
    - Anticipated regulatory filing for vatalanib in CRC is becoming increasingly unlikely following disappointing CONFIRM-1 and CONFIRM-2 interim results
    - Recent update of vatalanib in Gleevec-resistant GIST patients
    - Recent update of the Phase II GOAL Study in NSCLC
    - Novartis/Schering AG adopt an aggressive approach, investigating vatalanib in a number of indications
  - Datamonitor Comments
    - Vatalanib unlikely to compete with Avastin in the metastatic CRC market
    - Schering AG' s and particularly Novartis' s prior oncology experience will be invaluable to vatalanib
    - Novartis and Schering AG are determined to exploit any commercial potential vatalanib may have
- Sanofi Aventis/Regeneron' s VEGF-Trap
  - Drug Profile
  - Clinical Trial Data
    - VEGF-Trap enters Phase III for ovarian cancer
    - VEGF-Trap in Phase II for NSCLC and RCC
    - Selecetd Phase I clinical studies in solid tumors
    - VEGF-Trap demonstrates similar side effects to Avastin
  - Datamonitor Comments
    - Fierce competition with Avastin in the ovarian cancer market
    - Presence in oncology field will aid commercialisation of VEGF-Trap
- Forecasts
- Datamonitor drug assessment summary
CHAPTER 7 PIPELINE SINGLE-TARGET SIGNAL TRANSDUCTION INHIBITORS ANALYSIS & FORECASTS
- Pipeline overview
- Amgen' s Vectibix (panitumumab; ABX-EGF)
  - Drug Profile
    - Overexpression of EGFR makes an ideal target for Vectibix development
  - Clinical Trial Data
    - Vectibix is approved for metastatic CRC and showing promise in a range of other treatment settings
    - Addition of Vectibix does not enhance standard chemotherapy in NSCLC
    - Vectibix fails as a single agent in RCC
    - Main side effect is a potential indicator of Vectibix activity
  - Datamonitor Comments
    - Humanized nature of Vectibix will challenge its competitor EGFR inhibitors
    - Vectibix versus Erbitux
    - Third-line setting for metastatic CRC is a good place to start
    - Amgen should focus on combination regimens while considering the intellectual property issues
    - Potential development of a biomarker for Vectibix
    - Amgen' s presence will ensure success with profitability increasing by targeting earlier lines of therapy
- Schering-Plough' s Sarasar (Lonafarnib)
  - Drug Profile
  - Clinical Trial Data
    - Main focus of Sarasar development in MDS, where greatest antitumor activity is shown
    - Farnesyl transferase inhibitors predominately in hematological disorders
    - Lack of efficacy has led to termination of pivotal Phase III trial in NSCLC
    - Lack of clinical data makes it difficult to judge Sarasar' s potential in breast cancer
    - Initiation of a Phase II trial in Ovarian Cancer
    - Benefit shown in advanced head and neck cancer, although no further trials have been announced
    - Currently no further trials planned for pancreatic cancer, urothelial carcinoma and colorectal cancer
    - Mild toxicity in the majority of patients, although grade 3 events do occur
  - Datamonitor Comments
    - Sarasar' s chances for approval will be delayed beyond 2007
    - Sarasar racing against Johnson & Johnson' s Zarnestra as the first farnesyl transferase inhibitor to reach the market
    - Presence in oncology market will aid commercialization of Sarasar
- Abbott Laboratories' Xinlay (atrasentan)
  - Drug Profile
    - Xinlay' s target receptor plays a key role in cancer cell proliferation
  - Clinical Trial Data
    - FDA do not approve Xinlay for prostate cancer
    - Other trials
  - Datamonitor Comments
    - Despite its rejection by the FDA, Xinlay' s future may still be promising
    - Abbott' s favorable position in the prostate cancer market will be invaluable
- Wyeth' s Temsirolimus (CCI-779)
  - Drug Profile
    - Temsirolimus inhibits a key pathway in tumor cell proliferation
  - Clinical Trial Data
    - Promising Phase III results in RCC reported at ASCO 2006
    - Temsirolimus showing promise in mantle cell lymphoma
    - Temsirolimus trial in breast cancer is discontinued
    - Combination studies with temsirolimus initiated in malignant melanoma
    - Combination studies with temsirolimus initiated in glioblastome multiforme
    - Temsirolimus as a monotherapy
    - Mild toxicity means temsirolimus is well tolerated
  - Datamonitor Comments
    - Targeting poor prognosis patients may eventually accelerate temsirolimus' expansion within RCC
    - Temsirolimus will have to face Velcade in the MCL market
    - Prior commercialization of Mylotarg and Neumega will provide Wyeth with valuable insight into the oncology market
- Janssen/Johnson & Johnson' s Zarnestra (tipifarnib)
  - Drug Profile
  - Clinical Trial Data
    - Following rejection of NDA, the FDA requires Phase III data for Zarnestra in AML before regulatory approval can be considered
    - Zarnestra shows activity in MDS
    - Zarnestra development in breast cancer remains in Phase II trials
    - Following modest activity in brain cancer, further trials have been initiated
    - Initiation of Phase II trials in large granular lymphocyte leukemia and malignant melanoma
    - Negative Phase III trial results caused termination of development in solid tumors
    - Phase I trial is ongoing for Zarnestra in combination with chemotherapy in advanced NSCLC
    - Mild toxicity is particularly significant since Zarnestra' s main indication is for elderly AML patients where quality of life is a major issue
  - Datamonitor Comments
    - Schering-Plough' s Sarasar catching up with Zarnestra as the first farnesyl transferase inhibitor to reach the market
    - Johnson & Johnson limiting Zarnestra' s target population in the short term
    - Johnson & Johnson' s experience will be invaluable to Zarnestra
- YM Bioscience' s TheraCIM (Theraloc; Nimotuzumab)
  - Drug Profile
  - Clinical Trial Data
    - Phase III for pediatric pontine (brain stem) glioma
    - Phase II pediatric trial demonstrated activity
    - Positive efficacy and favorable toxicity data for Phase II trial results of TheraCIM
  - Datamonitor Comments
    - Phase III trial results required to verify the efficacy of this agent
- Forecasts
- Datamonitor drug assessment summary
CHAPTER 8 PIPELINE MULTI-TARGETED INHIBITORS ANALYSIS & FORECASTS
- Pipeline overview
- GlaxoSmithKline' s Tykerb/Tycerb (Lapatinib)
  - Drug Profile
    - Tykerb is unique among the EGFR inhibitors, targeting two receptor tyrosine kinases
  - Clinical Trial Data
    - Tykerb set to penetrate the breast cancer market
    - Tykerb did not meet the primary endpoint in mRCC Phase III study
    - Tykerb monotherapy shows no activity in BTC but shows promise in HCC
    - Tykerb appears to have little activity in SCCHN
    - Other clinical trials
  - Datamonitor Comments
    - Tykerb' s dual ErbB targeting mechanism will lead to a significant patient potential
    - Tykerb and capecitabine combination looking to become the gold-standard for second-line metastatic beast cancer
    - Tykerb' s ability to threaten Herceptin still hangs in the balance
    - GSK also looks to secure a future for Tykerb as part of combination regimens
    - GSK' s limited oncology portfolio will be bolstered by the arrival of Tykerb
- ChemGenex Pharmaceuticals' Ceflatonin (CGX-635, Myelostat)
  - Drug Profile
  - Clinical Trial Data
    - Ceflatonin aims to restore Gleevec sensitivity in CML patients
  - Datamonitor Comments
    - Despite convincing clinical benefit, Ceflatonin will face strong competition from Bristol-Myers Squibb' s Sprycel and Novartis' s Tasigna
- Ipsen' s Somatuline (Lanreotide)
  - Drug Profile
  - Clinical Trial Data
    - Somatuline enters Phase III for entero-pancreatic endocrine tumors
    - Somatuline in neuroendocrine tumors
  - Datamonitor Comments
    - Somatuline will benefit from its marketed status
    - Somatuline may end up competing with Sutent in neuroendocrine tumors
- Novartis' s Tasigna (Nilotinib, AMN-107)
  - Drug Profile
  - Clinical Trial Data
    - Tasigna receives fast track and orphan drug status for Gleevec-resistant CML
    - Promising Phase II interim data reported
    - Only one BCR-ABL mutation is insensitive to Tasigna
    - Tasigna shows promise for Gleevec-resistant metastatic GIST patients
  - Datamonitor Comments
    - Tasigna ready to challenge Bristol-Myers Squibb' s already approved Sprycel
    - Novartis looking to expand its leading role in the CML therapy market
- AstraZeneca' s Zactima (Vandetanib; ZD6474)
  - Drug Profile
  - Clinical Trial Data
    - Zactima granted Orphan Drug designation and Fast Track status for Thyroid cancer
    - Following promising Phase II results, a Phase III trial of Zactima in combination with Taxotere has begun in NSCLC
    - Zactima shown to be more effective than Gefitinib in NSCLC
    - Initiation of Phase II trial in Glioma
  - Datamonitor Comments
    - Zactima set to enjoy a monopoly of thyroid cancer niche market
    - Only two other agents share the multi-targeted characteristics of Zactima
    - Zactima will need to overcome Tarceva in the NSCLC market
    - AstraZeneca' s strength in the oncology market will be key in Zactima' s success
- Eli Lilly' s Enzastaurin (LY317615)
  - Drug Profile
  - Clinical Trial Data
    - Enzastaurin granted Orphan Drug status by the EMEA and FDA
    - Enzastaurin in Phase III for Glioblastoma Multiforme
    - Enzastaurin in Phase III for B-Cell Lymphoma
    - Other clinical trials
  - Datamonitor Comments
    - Enzastaurin fulfills significant unmet needs in recurrent GBM setting
    - Eli Lilly adopt a risky stragtegy for enzastaurin in BCL
    - Eli Lilly
- Cephalon' s Lestaurtinib (CEP-701)
  - Drug Profile
  - Clinical Trial Data
  - Datamonitor Comments
    - Lestaurtinib may be the first in its class to reach the market
    - Cephalon' s recent acquisition of Trisenox will provide invaluable experience of the leukemia market
- Forecasts
- Datamonitor drug assessment summary
CHAPTER 9 PIPELINE CELL CYCLE AND APOPTOSIS TARGETED AGENTS ANALYSIS & FORECASTS
- Pipeline overview
- Genta' s Genasense (Oblimersen)
  - Drug Profile
    - Despite termination of Genta' s agreement with Sanofi-Aventis, Genasense remains in development for a multitude of indications
  - Clinical Trial Data
    - Benefits of Genasense in CLL may not be enough to offset the addition of significant toxicity
    - Long-term survival results of Genasense in malignant melanoma are of significance
    - Disappointing Phase III trial results in multiple myeloma means status of further development is unclear
    - Early-phase benefits of Genasense in AML require confirmation in Phase III clinical trial
    - Promise shown in combination with rituximab in NHL, but randomized trials have yet to be initiated
    - Lack of clinical data in NSCLC makes it difficult to judge Genasense' s potential
    - Encouraging Phase II results in prostate cancer, though Phase III trials have yet to be initiated
    - Ongoing Phase II trial in SCLC will determine if patient benefit counters additional toxicity
    - Genasense did not enhance activity of standard interferon-alfa in RCC
    - Other trials
  - Datamonitor Comments
    - Approval of Genasense is looking increasingly unlikely
    - Termination of agreement with Sanofi-Aventis is a major setback for Genta
- Telik' s Telcyta (TLK286)
  - Drug Profile
    - Telcyta: a small molecule prodrug with dual antitumor activity developed using Telcyta' s TRAP technology
  - Clinical Trial Data
    - Telcyta has Fast Track status for both NSCLC and Ovarian cancer
    - Telcyta in NSCLC
    - Telcyta in ovarian cancer
    - Telcyta shows some activity as a single agent in breast cancer, although final Phase II results have yet to be published
  - Datamonitor Comments
    - Telik was unfortunate to use Iressa as a comparator in Telcyta' s ASSIST-2 trial
    - Penetrating the second- and third-line ovarian cancer market
    - Without a partner, Telik will struggle to commercialize Telcyta
- Celtic Pharma/Xenova' s TransMID (XR-311)
  - Drug Profile
    - TransMID' s target is highly relevant in glioma
  - Clinical Trial Data
    - Encouraging Phase II results, active clinical trial program and Fast Track designation will drive development of TransMID
  - Datamonitor Comments
    - Cumbersome infusion schedule and administration may detract from TransMID' s broad clinical benefit
    - Although Xenova has secured several marketing partnerships, a glaring omission is one in the lucrative US market
- Sanofi-Aventis' s Alvocidib (Flavopiridol)
  - Drug Profile
  - Clinical Trial Data
    - Continuous infusion dosing schedules fail to demonstrate clinical activity
    - Modified dosing regimen drives further development in CLL
    - Alvocidib proves ineffective in hepatocellular carcinoma
    - Initiation of a Phase II trial involving alvocidib in pancreatic cancer
  - Datamonitor Comments
    - Alvocidib' s checkered history leaves KOLs cynical about its future clinical potential
    - Alvocidib may show more promise as part of a combination regimen
    - Presence in oncology field will aid commercialization of alvocidib
- Novogen' s Phenoxodiol
  - Drug Profile
  - Clinical Trial Data
    - Phenoxodiol' s Fast Track status in Ovarian Cancer
    - The OVATURE trials
    - Initiation of a Phase I/II trial for Phenoxodiol plus Taxotere in ovarian cancer
    - Phenoxodiol in Phase I for a variety of solid tumors
  - Datamonitor Comments
    - Toxicity will be the key factor for phenoxodiol' s success
    - Sanofi-Aventis as a marketing partner?
- Forecasts
- Datamonitor drug assessment summary
CHAPTER 10 PIPELINE EPIGENETIC MODULATORS ANALYSIS & FORECASTS
- Pipeline overview
- Merck' s Zolinza (Vorinostat, SAHA)
  - Drug Profile
  - Clinical Trial Data
    - Zolinza granted Priority Review for CTCL following promising Phase IIb results
    - FDA granted Orphan Drug designation for multiple myeloma
    - Zolinza in Phase III trial for malignant pleural mesothelioma
    - Other clinical trials
  - Datamonitor Comments
    - Zolinza will serve to increase Merck' s oncology portfolio
    - Merck conscious to not limit the use of Zolinza to just CTCL and myeloma
    - Zolinza may face competition from Gloucester Pharmaceuticals' romidepsin
- Gloucester Pharmaceuticals' Romidepsin (FK-228, depsipeptide)
  - Drug Profile
    - Broad range of HDAC inhibition should theoretically provide increased efficacy
  - Clinical Trial Data
    - Romidepsin has fast track status and orphan drug status for CTCL
    - Encouraging results in CTCL require replication in a Phase III clinical trial
    - Romidepsin also showing promise in PTCL
    - Romidepsin in Phase II for HRPC despite lack of preclinical evidence for this indication
  - Datamonitor Comments
    - Romidepsin may have difficulty competing with Merck' s Zolinza in the CTCL market
    - Further evaluation is needed to establish the clinical activity of combination therapy using HDAC inhibitors with cytotoxic drugs
    - Commercial success of romidepsin will rely on Gloucester Pharmaceuticals collaborating with large pharma
- Forecasts
- Datamonitor drug assessment summary
CHAPTER 11 PIPELINE IMMUNOMODULATORY AND IMMUNOCONJUGATED THERAPEUTICS ANALYSIS & FORECASTS
- Pipeline overview
- Wilex' s Rencarex (WX-G250)
  - Drug Profile
    - MN/CA IX Antigen - A Highly Specific Tumor Target
    - Mode of Action of Rencarex - ADCC
  - Clinical Trial Data
    - Rencarex in Phase III for non-metastatic RCC (the ARISER trial)
    - Completed Phase I & II trials for metastatic RCC
  - Datamonitor Comments
    - Rencarex may face a number of hurdles
- Genmab' s Ofatumumab (HuMax-CD20)
  - Drug Profile
  - Clinical Trial Data
    - Genmab hoping ofatumumab will demonstrate a preferred efficacy profile over Rituxan in the clinic
    - Ofatumumab receives fast track status for CLL and enters a Phase III trial
    - Genmab initiate a pivotal trial in NHL
  - Datamonitor Comments
    - Genmab should look to compare ofatumumab with Rituxan in a Phase III trial
    - Commercial success of ofatumumab will rely on Genmab collaborating with large pharma
- Forecasts
- Datamonitor drug assessment summary
CHAPTER 12 COMMERCIAL IMPACT & LIFECYCLE MANAGEMENT: CASE STUDIES
- Introduction
- Case study one
  - Clinical, developmental and commercial challenges to combining molecular targeted therapies
    - How to optimally utilize molecular targeted therapies in the context of combinatorial regimens
    - Intellectual property implications associated with combining targeted therapies
    - Lessons to be learnt from already marketed targeted therapies
    - Differences and similarities between monoclonal antibodes and small molecules
    - Effectively demonstrating the clinical and pharamcoeconomic value of combinatorial MTT strategies is critical
- Case study two
  - Comparing marketed and pipeline MTTs: The evolving trends
    - Segmentation of MTTs by structural class
    - Segmentation of MTTs by indication
    - Approval paths experienced by the marketed MTTs
    - Developing a targeted therapy for a niche tumor over one of the ' big four' tumor types - Which strategy should Pharma pursue?
APPENDIX A - MARKET DATA & MAJOR BRAND KEY FACTS
- L1X3 (antineoplastic monoclonal antibodies) class market data
- 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
- Five Major European Markets (EU5) Forecasts
- Seven Major Markets 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
- Abbreviations
- Contributing experts
- Bibliography
- About Datamonitor
  - About Datamonitor Healthcare
  - About the Oncology analysis team
- Disclaimer
- List of Tables
  - Table 1: Molecular targeted therapies in preregistration, 2006
  - Table 2: Molecular targeted therapies in Phase III development, 2006
  - Table 3: Pipeline molecular targeted therapies by development phase and class of drug, 2006
  - Table 4: Pipeline molecular targeted therapies by indication, 2006
  - Table 5: Specific target/targets with two candidates in the pipeline, 2006
  - Table 6: Specific target/targets with three or more candidates in the pipeline, 2006
  - Table 7: Number of products in the pipeline targeting key molecular drivers of cancer, 2006
  - Table 8: Companies with two candidates in the molecular targeted therapies pipeline, 2006
  - Table 9: Companies with three candidates in the molecular targeted therapies pipeline, 2006
  - Table 10: Companies with four or more candidates in the molecular targeted therapies pipeline, 2006
  - Table 11: Pfizer' s marketed oncology portfolio, 2006
  - Table 12: Pfizer' s molecular targeted cancer therapies portfolio, 2006
  - Table 13: Novartis' marketed oncology portfolio, 2006
  - Table 14: Novartis' molecular targeted cancer therapies portfolio, 2006
  - Table 15: GSK' s marketed oncology portfolio, 2006
  - Table 16: GSK' s molecular targeted cancer therapies portfolio, 2006
  - Table 17: Late-phase pipeline targeted therapies sales forecasts for the seven major markets ($m), 2006-2015
  - Table 18: Datamonitor drug assessment summary for late-phase pipeline molecular targeted cancer therapies, 2006
  - Table 19: Common mutations involved in tumor development
  - Table 20: Forecast incidence of cancer across the seven major markets, 2005-2013
  - Table 21: Examples of naturally occurring angiogenesis stimulators
  - Table 22: Recently approved multi-targeted inhibitors, 2006
  - Table 23: Current targeted therapy marketed products, 2006 (1 of 2)
  - Table 24: Current targeted therapy marketed products, 2006 (1 of 2)
  - Table 25: Targeted therapies sales in the seven major markets, 2005
  - Table 26: Clinical pipeline for Nexavar, 2006
  - Table 27: Clinical pipeline for Sprycel, 2006
  - Table 28: Summary of Phase II Sprycel clinical trial results
  - Table 29: Clinical pipeline for Sutent, 2006
  - Table 30: Approved indications for Rituxan in the US and EU, 2006
  - Table 31: Late-phase pipeline angiogenesis inhibitors, 2006
  - Table 32: Phase II pipeline angiogenesis inhibitors, 2006
  - Table 33: Phase I pipeline angiogenesis inhibitors, 2006
  - Table 34: Ongoing clinical trials involving AZD2171, 2006
  - Table 35: Ongoing clinical trials involving pazopanib, 2006
  - Table 36: Ongoing clinical trials involving vatalanib, 2006
  - Table 37: Ongoing clinical trials involving VEGF-Trap, 2006
  - Table 38: Forecasting assumptions for late-phase angiogenesis inhibitors, 2006
  - Table 39: Angiogenesis inhibitors sales forecasts ($m), 2006-2015
  - Table 40: Research/clinical and commercial attractiveness of pipeline angiogenesis inhibitors, 2006
  - Table 41: Late-phase pipeline single-target signal transduction inhibitors, 2006
  - Table 42: Phase II pipeline single-target signal transduction inhibitors, 2006
  - Table 43: Phase I pipeline single-target signal transduction inhibitors, 2006
  - Table 44: Ongoing clinical trials involving Vectibix, 2006
  - Table 45: Ongoing clinical trials involving Sarasar, 2006
  - Table 46: Ongoing clinical trials involving Xinlay, 2006
  - Table 47: Historical development of Xinlay, 1994-2005
  - Table 48: Ongoing Phase II/III trials involving temsirolimus, 2006
  - Table 49: Ongoing clinical trials involving Zarnestra, 2006
  - Table 50: Phase I/II trial involving Nexavar, Tarceva, Temsirolimus and Zarnestra, 2006
  - Table 51: Forecasting assumptions for late-stage pipeline single-target signal transduction inhibitors (1 of 2)
  - Table 52: Forecasting assumptions for late-stage pipeline single-target signal transduction inhibitors (2 of 2)
  - Table 53: Single-target signal transduction inhibitors sales forecasts ($m), 2006-2015
  - Table 54: Research/clinical and commercial attractiveness of pipeline single-target signal transduction inhibitors (1 of 2)
  - Table 55: Research/clinical and commercial attractiveness of pipeline single-target signal transduction inhibitors (2 of 2)
  - Table 56: Late-phase pipeline multi-targeted inhibitors, 2006
  - Table 57: Phase II pipeline multi-targeted inhibitors, 2006
  - Table 58: Phase I pipeline multi-targeted inhibitors, 2006
  - Table 59: Ongoing breast cancer clinical trials involving Tykerb, 2006
  - Table 60: Ongoing non-breast cancer clinical trials involving Tykerb, 2006
  - Table 61: Summary of key Tykerb breast cancer clinical trials, 2006
  - Table 62: Ongoing clinical trials involving Ceflatonin, 2006
  - Table 63: Ongoing trials involving Somatuline, 2006
  - Table 64: Ongoing clinical trials involving Tasigna, 2006
  - Table 65: Zactima' s multiple anticancer targets
  - Table 66: Ongoing clinical trials involving Zactima
  - Table 67: Ongoing clinical trials involving enzastaurin, 2006
  - Table 68: Ongoing clinical trials involving lestaurtinib
  - Table 69: Forecasting assumptions for late-stage pipeline multi-targeted inhibitors (1 of 2)
  - Table 70: Forecasting assumptions for late-stage pipeline multi-targeted inhibitors (2 of 2)
  - Table 71: Multi-targeted inhibitors sales forecasts ($m), 2006-2015
  - Table 72: Research/clinical and commercial attractiveness of pipeline multi-targeted inhibitors (1 of 2)
  - Table 73: Research/clinical and commercial attractiveness of pipeline multi-targeted inhibitors (2 of 2)
  - Table 74: Late-phase pipeline cell cycle and apoptosis targeted agents, 2006
  - Table 75: Phase II pipeline cell cycle and apoptosis targeted agents, 2006
  - Table 76: Phase I pipeline cell cycle and apoptosis targeted agents, 2006
  - Table 77: Ongoing clinical trials involving Genasense, 2006
  - Table 78: Ongoing clinical trials involving Telcyta, 2006
  - Table 79: NSCLC clinical trial data summary for Telcyta, 2006
  - Table 80: Key Phase III trials of Telcyta for ovarian cancer, 2006
  - Table 81: Ongoing clinical trials involving TransMID, 2006
  - Table 82: Ongoing clinical trials involving alvocidib, 2006
  - Table 83: Ongoing clinical trials involving phenoxodiol, 2006
  - Table 84: Forecasting assumptions for late-stage pipeline cell cycle and apoptosis targeted agents (1 of 2)
  - Table 85: Forecasting assumptions for late-stage pipeline cell cycle and apoptosis targeted agents (2 of 2)
  - Table 86: Cell cycle and apoptosis targeted agents sales forecasts ($m), 2006-2015
  - Table 87: Research/clinical and commercial attractiveness of pipeline cell cycle and apoptosis targeted agents
  - Table 88: Late-phase pipeline epigenetic modulators, 2006
  - Table 89: Phase II pipeline epigenetic modulators, 2006
  - Table 90: Phase I pipeline epigenetic modulators, 2006
  - Table 91: Ongoing clinical trials involving Zolinza, 2006
  - Table 92: Ongoing clinical trials involving romidepsin, 2006
  - Table 93: Zolinza forecasting assumptions
  - Table 94: Zolinza sales forecasts ($m), 2006-2015
  - Table 95: Research/clinical and commercial attractiveness of Zolinza
  - Table 96: Late-phase pipeline immunomodulatory and immunoconjugated therapeutics, 2006
  - Table 97: Phase II pipeline immunomodulatory and immunoconjugated therapeutics, 2006
  - Table 98: Phase I pipeline immunomodulatory and immunoconjugated therapeutics, 2006
  - Table 99: Ongoing clinical trial involving Rencarex, 2006
  - Table 100: Ongoing clinical trial involving ofatumumab, 2006
  - Table 101: Forecasting assumptions for late-phase immunomodulatory and immunoconjugated therapeutics
  - Table 102: Late-phase immunomodulatory and immunoconjugated therapeutics sales forecasts ($m), 2006-2015
  - Table 103: Research/clinical and commercial attractiveness of the late-phase immunomodulatory and immunoconjugated therapeutics
  - Table 104: Phase I/II trial involving Nexavar, Tarceva, Temsirolimus and Zarnestra in GBM or gliosarcoma patients, 2006
  - Table 105: Examples of combinatorial approaches of MAbs with chemotherapy
  - Table 106: Comparative characteristics of small molecules and MAbs
  - Table 107: Single agents versus multiple agents in combination
  - Table 108: Marketed molecular targeted cancer therapies, 2006
  - Table 109: Rituxan: key facts
  - Table 110: Herceptin: key facts
  - Table 111: Campath: key facts
  - Table 112: Mylotarg: key facts
  - Table 113: Bexxar: key facts
  - Table 114: Avastin: key facts
  - Table 115: Erbitux: key facts
  - Table 116: Zevalin: key facts
  - Table 117: Gleevec: key facts
  - Table 118: Targretin: key facts
  - Table 119: Iressa: key facts
  - Table 120: Velcade: key facts
  - Table 121: Tarceva: key facts
  - Table 122: Sprycel: key facts
  - Table 123: Nexavar: key facts
  - Table 124: Sutent: key facts
  - Table 125: Ontak: key facts
  - Table 126: Forecasts for marketed targeted therapies for the US ($m), 2005-2015
  - Table 127: Forecasts for marketed targeted therapies for Japan ($m), 2005-2015
  - Table 128: Forecasts for marketed targeted therapies for France ($m), 2005-2015
  - Table 129: Forecasts for marketed targeted therapies for Germany ($m), 2005-15
  - Table 130: Forecasts for marketed targeted therapies for Italy ($m), 2005-15
  - Table 131: Forecasts for marketed targeted therapies for Spain ($m), 2005-15
  - Table 132: Forecasts for marketed targeted therapies in the UK ($m), 2005-15
  - Table 133: Forecasts for marketed targeted therapies for the EU5 ($m), 2005-2015
  - Table 134: Forecasts for marketed targeted therapies for the seven major markets ($m), 2005-2015
  - Table 135: Datamonitor drug assessment parameters
  - Table 136: Abbreviations used in Pipeline/Commercial Insight: Molecular Targeted Cancer Therapies (1 of 2)
  - Table 137: Abbreviations used in Pipeline/Commercial Insight: Molecular Targeted Cancer Therapies (2 of 2)
- List of Figures
  - Figure 1: Pipeline molecular targeted therapies by development phase and class of drug, 2006
  - Figure 2: Pipeline molecular targeted therapies by class of drug, 2006
  - Figure 3: Pipeline molecular targeted therapies by development phase, 2006
  - Figure 4: Angiogenesis inhibitors by developmental phase, 2006
  - Figure 5: Single-target signal transduction inhibitors by developmental phase, 2006
  - Figure 6: Multi-targeted inhibitors by developmental phase, 2006
  - Figure 7: Cell cycle and apoptosis targeted agents by developmental phase, 2006
  - Figure 8: Epigenetic inhibitors by developmental phase, 2006
  - Figure 9: Immunomodulatory and immunoconjugated therapeutics by developmental phase, 2006
  - Figure 10: Pipeline molecular targeted therapies by solid tumor indication, 2006
  - Figure 11: Pipeline molecular targeted therapies by hematological malignancy, 2006
  - Figure 12: Number of products in the pipeline targeting key molecular drivers of cancer, 2006
  - Figure 13: Companies with four or more candidates in the molecular targeted therapies pipeline, 2006
  - Figure 14: Pipeline angiogenesis inhibitors sales forecasts for the seven major markets ($m), 2006-2015
  - Figure 15: Pipeline single-target signal transduction inhibitors sales forecasts for the seven major markets ($m), 2006-2015
  - Figure 16: Pipeline multi-targeted inhibitors sales forecasts for the seven major markets ($m), 2006-2015
  - Figure 17: Pipeline cell cycle and apoptosis targeted agents sales forecasts for the seven major markets ($m), 2006-2015
  - Figure 18: Pipeline epigenetic modulators sales forecasts for the seven major markets ($m), 2006-2015
  - Figure 19: Pipeline immunomodulatory and immunoconjugated therapeutics sales forecasts for the seven major markets ($m), 2006-2015
  - Figure 20: Datamonitor drug assessment summary for pipeline angiogenesis inhibitors, 2006
  - Figure 21: Datamonitor drug assessment summary for pipeline single-target signal transduction inhibitors, 2006
  - Figure 22: Datamonitor drug assessment summary for pipeline multi-targeted inhibitors, 2006
  - Figure 23: Datamonitor drug assessment summary for pipeline cell cycle and apoptosis targeted agents, 2006
  - Figure 24: Datamonitor drug assessment summary for epigenetic modulators, 2006
  - Figure 25: Datamonitor drug assessment summary for immunomodulatory and immunoconjugated therapeutics, 2006
  - Figure 26: Global oncology sales ($m), 2002-09
  - Figure 27: Oncology pipeline including supportive care, 2006
  - Figure 28: Forecast incidence of cancer across the seven major markets, 2005-2013
  - Figure 29: Combined incidence for breast, lung, prostate and colorectal cancer rises with age in seven major markets, 2003
  - Figure 30: Incidence increases, while the rate of cure and death reduces disease prevalence
  - Figure 31: Point prevalence for colorectal and lung cancer differs markedly despite similar rates of incidence
  - Figure 32: Unmet needs in cancer, 2006
  - Figure 33: The process of tumor angiogenesis
  - Figure 34: Approaches to inhibition of VEGF signaling
  - Figure 35: Angiogenesis inhibitors sales forecasts ($m), 2006-2015
  - Figure 36: Research/clinical and commercial attractiveness of pipeline angiogenesis inhibitors, 2006
  - Figure 37: Single-target signal transduction inhibitors sales forecasts ($m), 2006-2015
  - Figure 38: Research/clinical and commercial attractiveness of pipeline single-target signal transduction inhibitors, 2006
  - Figure 39: Design of Phase III Tykerb plus capecitabine versus capecitabine alone trial
  - Figure 40: Multi-targeted inhibitors sales forecasts ($m), 2006-2015
  - Figure 41: Research/clinical and commercial attractiveness of pipeline multi-targeted inhibitors
  - Figure 42: Telcyta' s mechanism of action
  - Figure 43: TransMID' s mode of action
  - Figure 44: Cell cycle and apoptosis targeted agents sales forecasts ($m), 2006-2015
  - Figure 45: Research/clinical and commercial attractiveness of pipeline cell cycle and apoptosis targeted agents
  - Figure 46: Zolinza sales forecasts ($m), 2006-2015
  - Figure 47: Research/clinical and commercial attractiveness of Zolinza
  - Figure 48: Rencarex induced ADCC
  - Figure 49: Rencarex Phase II results: median survival
  - Figure 50: Late-phase immunomodulatory and immunoconjugated therapeutics sales forecasts ($m), 2006-2015
  - Figure 51: Research/clinical and commercial attractiveness of the late-phase immunomodulatory and immunoconjugated therapeutics, 2006
  - Figure 52: Number of marketed MAbs and small molecules, 2006
  - Figure 53: Number of late-phase MAbs and small molecules, 2006
  - Figure 54: Number of marketed molecular targeted therapies for solid tumors and hematological malignancies, 2006
  - Figure 55: Number of late-phase molecular targeted therapies for solid tumors and hematological malignancies, 2006
  - Figure 56: Number of molecular targeted therapies approved in the ' big four' tumor types, 2006
  - Figure 57: Number of late-phase molecular targeted therapies in the ' big four' tumor types, 2006
  - Figure 58: Marketed molecular targeted therapies by indication, 2006
  - Figure 59: Phase I, II and III molecular targeted therapies by indication, 2006
  - Figure 60: Approval paths of the marketed molecular targeted therapies
  - Figure 61: Advantages and disadvantages of developing an MTT in one of the ' Big Four' tumor types
  - Figure 62: Advantages and disadvantages of developing an MTT in a niche tumor type
  - Figure 63: Example of Datamonitor drug assessment scorecard
  - Figure 64: Example of Datamonitor drug assessment graph

Pipeline/Commercial Insight: Molecular Targeted Cancer Therapies - More drugs on the market, more targets in the pipeline

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