治療用癌ワクチン市場動向

Abstract

Overview

Introduction

Unmet needs across the cancer market remain high, with most therapies conferring low levels of specificity and high toxicity. Therapeutic cancer vaccines offer an attractive therapeutic addition, delivering treatment of high specificity, low toxicity and prolonged activity. However, despite years of R&D, a reproducible survival benefit has proved elusive, leaving the market wide open.

Scope

• Research and analysis of the cancer vaccines pipeline with in-depth clinical and commercial assessment of Phase III candidates, plus expert opinion
• Seven major pharmaceutical market sales forecasts to 2015 for key pipeline candidates incorporating product specific assumptions and events
• Segmentation and examination of product pipeline by phase, technology platform, vaccine specificity, indication and developer
• Insight and analysis of clinical, regulatory, pharmacoeconomic and strategic issues that challenge the path to commercialization of a cancer vaccine

Highlights

105 different pipeline cancer vaccines have been identified of which 14 are in late-phase development. These existing candidates have a forecast sales potential of up to $3.1 billion in the seven major pharmaceutical markets by 2015.

Despite Dendreon' s Provenge preregistration status, skepticism still surrounds the use of dendritic cells as a viable technology platform. Indeed, an entirely new set of clinical and strategic issues has been brought to light across the spectrum of cancer vaccine development classes.

While personalized immunotherapies offer greater levels of specificity and lower toxicity, generalized alternatives should facilitate production, help achieve economies of scale and offer broader utility in a range of tumor types. It is therefore not suspiring that these ' off-the-shelf' products dominate the current pipeline.

Reasons to Purchase

• Acquire a detailed appreciation and impartial perspective of the entire cancer vaccine developmental pipeline
• Identify the key therapeutic cancer vaccines in late-phase development based on sales forecasts to 2015 and drug assessment methodology
• Consider, assess and react to opportunities and risks for cancer vaccines within the oncology market

Table of Contents

• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of analysis
  • Key metrics
• CHAPTER 2 PIPELINE DYNAMICS
  • Pipeline overview
    • Therapeutic cancer vaccines in late-phase development
    • Therapeutic cancer vaccines in Phase II development
    • Therapeutic cancer vaccines in Phase I development
  • Pipeline by developmental phase and class
    • There are over 100 different therapeutic cancer vaccines in the clinical developmental pipeline
      • Antigen-specific vaccines account for over two-thirds of the current cancer vaccine pipeline
      • Segmentation of vaccines by developmental phase reflects high attrition rate in oncology drug development
  • Pipeline by technology platform
    • Lack of precedent is reflected by diversity of technology platforms
  • Pipeline by vaccine specificity
    • As expeceted, generalized vaccines dominate over personalized therapies
      • Generalized cancer vaccines represent nearly three quarters of the pipeline
  • Pipeline by indication
    • Cancer vaccines are being investigated in 18 different tumor types
      • Melanoma is the leading indication for vaccine development while RCC, another immunologically driven malignancy, is gaining ground
      • As expected, the ' big four' tumor types feature heavily in the current cancer vaccine pipeline
      • Vaccines directed against solid tumors outnumber those targeting the hematological malignancies
      • The 14 Phase III and preregistered vaccines target eight different tumor types
  • Pipeline by company
    • Developmental pipeline dominated by small pharma/biotech players
    • Only 14 companies/institutes have more than one candidate in the cancer vaccine developmental pipeline
      • Memorial Sloan-Kettering Cancer Center
      • Therion Biologics
      • A leading developer has yet to emerge
• CHAPTER 3 DISEASE OVERVIEW
  • 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 AND PIPELINE CLASSIFICATION
  • Active, specific immunotherapy
  • Overcoming immune tolerance is key to success
  • Types of targets for vaccine therapy
  • Classification of pipeline products
    • Antigen-specific vaccines
      • Tumor-associated antigen - carbohydrate
      • Peptide-based vaccine
      • Recombinant virus vaccine
      • Anti-idiotype vaccine
      • DNA vaccine
    • Polyvalent vaccines
      • Whole-cell vaccines
      • Tumor lysate vaccines
      • Shed antigens
      • Heat-shock proteins
    • Dendritic cell vaccines
    • Prophylactic vaccines
  • Relative merits of therapeutic cancer vaccines
• CHAPTER 5 NEW MARKET, NEW ISSUES
  • Integrating therapeutic cancer vaccines into current treatment paradigms
    • Cancer vaccines are likely to broaden existing treatment options not replace them
    • Immunosuppressive therapy can compromise the efficacy of a cancer vaccine
    • Cancer vaccines are likely to be most effective in the setting of minimal residual disease
    • Multiple vaccinations can induce development of strong neutralizing antibodies
    • Adjuvants can improve the immunogenicity of a cancer vaccine
  • Clinical trial design and surrogate endpoints for cancer vaccines
    • Clinical trial endpoints must adapt in line with changing needs
      • Multiple clinical trial endpoints are required to fully establish a vaccine' s therapeutic potential
      • Standard response criteria may have become somewhat redundant
      • Lack of adequate controls in the design of randomized clinical trials
    • Should immune monitoring be integral to assessing the efficacy of vaccine strategies?
      • Both cellular and humoral responses appear to be attractive methods for monitoring immune responses
      • To date, little correlation exists between immune response and clinical outcome
  • Strategic challenges facing the commercialization of cancer vaccines
    • Regulatory issues cloud the road to commercialization
      • FDA request for further clinical data led to cessation of Corixa US development of Melacine
    • Formulation and manufacturing of cancer vaccines can become a major cause for concern
      • M-Vax' s route to market hindered due to manufacturing and formulation considerations
    • Skepticism over cost-effectiveness hampers commercialization
      • Restrictive pricing and reimbursement policies may obstruct the potential uptake of an approved cancer vaccine
    • Wide range of indications under development makes it difficult to compare efficacies of each class of cancer vaccine
      • Datamonitor research has shown pipeline cancer vaccines to be in development for 18 different tumor types
  • Significant hurdles challenge the path to commercialization
• CHAPTER 6 ANTIGEN-SPECIFIC CANCER VACCINES ANALYSIS & FORECASTS
  • Pipeline overview
    • Late-phase pipeline of antigen-specific cancer vaccines
    • Phase II pipeline of antigen-specific cancer vaccines
    • Phase I pipeline of antigen-specific cancer vaccines
  • MGI Pharma Biologics' Amolimogene (Biotope-CD; ZYC101a)
    • Drug profile
    • Clinical trial data
      • Amolimogene edges closer to the market with a Phase III trial for cervical dysplasia
      • Amolimogene may be effective for anal dysplasia
      • Amolimogene may become the first DNA-based vaccine to reach the market
      • MGI Pharma will provide Amolimogene with valuable oncology experience
  • Pharmexa' s GV1001
    • Drug profile
    • Clinical trial data
      • Phase III trials for GV1001 in metastatic pancreatic cancer have been initiated and will recruit around 1,500 patients
      • Previous studies results warrent further development of GV1001 in a number of indications
      • GV1001 Phase II study in hepatocellular carcinoma has been initiated
      • Promising Phase I/II in NSCLC should encourage further development within the ' Big Four' tumor types
      • GV1001 with Temodar is a feasible combination for melanoma
      • GV1001 set to become the first telomerase-targeted vaccine to reach the market
      • GV1001 may struggle to achieve optimal market penetration without a more experienced oncology player
  • Bristol-Myers Squibb' s MDX-1379
    • Drug profile
    • Clinical trial data
      • MDX-1379 and ipilimumab Fast Tracked for malignant melanoma
      • If encouraging, results from an ongoing Phase III clinical trial will support a BLA
      • Phase II results demonstrate complete of partial responses for the MDX-1379 and ipilimumab combination in melanoma
      • Optimizing the risk-benefit ratio is paramount in progressing commercial development of MDX-1379
      • Partnership with Bristol-Myers Squibb will put Medarex at a significant advantage
  • Oxford BioMedica' s TroVax (MVA-h5T4)
    • Drug profile
    • Clinical trial data
      • Oxford BioMedica initiates Phase III (TRIST) trial for TroVax in combination with standard treatment for RCC
      • Humoral immune responses induced in the majority of CRC patients following vaccination with TroVax
      • With trials now beginning in breast and prostate cancer, TroVax may potentially gain approval within three of the ' Big Four' tumor types
      • TroVax on course to achieve first-to-market advantage
      • Approval for RCC likely to be a quicker route to market while horizontal expansion into three of the ' Big Four' tumor types will give TroVax a much wider patient base
      • TroVax must be competitively priced to ensure extensive uptake
      • Oxford BioMedica actively seeking a partner for commercializing TroVax
  • Progenics' GMK (GM2-KLH)
    • Drug profile
    • Clinical trial data
      • No further developments to the Phase III melanoma trial that was initiated in 2001
      • GMK proven inferior to standard treatment for stage III melanoma with high risk recurrence
      • Further development was based on earlier findings that GMK induces an antibody response in melanoma
      • Lack of commercialization experience and marketing partner will affect GMK' s potential
      • Negative Phase III data may have irrevocably damaged GMK' s potential
      • A superior strategy may be to shift investment to more lucrative opportunities
  • Receptor BioLogix' s Insegia (G17DT)
    • Drug profile
    • Clinical trial data
      • Combination of Insegia and Gemzar fails to meet primary endpoints in Phase III clinical trial for pancreatic cancer
      • Insegia monotherapy shows benefit in pancreatic cancer patients unable to receive chemotherapy
      • If Phase II benefits in gastric cancer are replicated in a Phase III study, Insegia' s commercial potential will be promising
      • Receptor BioLogix yet to initiate any further trials for Insegia
  • Accentia Biopharmaceuticals' BIOVAXID
    • Drug profile
    • Clinical trial data
      • BIOVAXID inches closer to approval in the US and European markets for follicular NHL
      • Phase III trial initiated in February 2000 is ongoing and continues to show favorable survival benefits of BIOVAXID
      • Possible association between a specific negative chromasomal translocation following vaccination and disease free survival in follicular NHL
      • Phase II results of BIOVAXID in mantle cell lymphoma are promising
      • BIOVAXID competing with FavId and MyVax to first-to-market status
      • BIOVAXID' s price-tag should reflect the anticipated competition and current treatment costs
  • Favrille' s FavId (Id-KLH)
    • Drug profile
    • Clinical trial data
      • FavId receives Fast Track status by the FDA for follicular NHL
      • Single-agent FavId demonstrates an objective response in indolent B-cell NHL
      • Favrille initiate FavId Phase III trial in DLBCL NHL
      • FavId competing with BIOVAXID and MyVax to reach the market first
      • Favrille' s lack of commercial experience will be a barrier to optimizing market penetration
  • Genitope' s MyVax (GTOP-99)
    • Drug profile
    • Clinical trial data
      • MyVax received Fast Track status for follicular NHL while Phase III clinical trial approaches completion
      • Phase II clinical trials show greater number of immune responses among previously untreated patients
      • Genitope initiate Phase I/II trial for MyVax in chronic lymphocytic leukemia
      • Follow up Phase II data of MyVax in mantle cell and diffuse large B-cell lymphoma warrants further investigation
      • Despite competition from BIOVAXID and FavId, MyVax increases its commercial potential by targeting an earlier stage treatment
      • With trials ongoing in CLL, MyVax may ultimately emerge as the most adaptable anti-idiotype vaccine
  • Comparison of anti-idiotype vaccines
  • Forecasts
  • Datamonitor drug assessment summary
• CHAPTER 7 POLYVALENT CANCER VACCINES ANALYSIS & FORECASTS
  • Pipeline overview
    • Late-phase pipeline of polyvalent cancer vaccines
    • Phase II pipeline of polyvalent cancer vaccines
    • Phase I pipeline of polyvalent cancer vaccines
  • AVAX Technologies' M-Vax
    • Drug profile
    • Clinical trial data
      • Financial constraints trouble M-Vax' s initial approval
      • M-Vax suffers a notable setback after AVAX is forced to address formulation issues
      • M-Vax re-enters Phase III development
      • Multiple hurdles challenge M-Vax' s future success
  • Cell Genesys' GVAX
    • Drug profile
    • Clinical trial data
      • Ongoing Phase III clinical trials need to confirm benefits of GVAX' s increased potency
      • High-dose GVAX demonstrates 13-month survival improvement over standard chemotherapy
      • Re-engineered second-generation GVAX confers increased potency in second round of Phase II clinical trials
      • Two-year survival data for GVAX in pancreatic cancer will encourage development for this indication
      • Phase II trial suggests GVAX is active in AML
      • Cell Genesys discontinues GVAX development for NSCLC and myeloma
      • GVAX' s approval for prostate cancer will be greatly anticipated
      • Cell Genesys will require an expansion of its marketing and distribution resources to optimize GVAX' s commercialization
  • Intracel' s OncoVAX
    • Drug profile
    • Clinical trial data
      • FDA grants Intracel SPA for pivotal Phase III study for OncoVAX
      • Earlier studies demonstrate OncoVAX significantly improves survival in stage II colon cancer
      • Stage II colon cancer is a good place to start for OncoVAX but line extensions will be key to continued success
      • OncoVAX is the only vaccine in Phase III for CRC but a number of other candidates exist in the pipeline
  • Antigenics' Oncophage (Vitespen; HSPPC-96)
    • Drug profile
    • Clinical trial data
      • Oncophage in development for a range of tumor types
      • Improved second-generation formulation facilitates use in early-stage disease
      • Promising Phase III results encourages further investigation in melanoma
      • Phase III study in RCC is halted after no increase in overall survival is achieved
      • Approval in other tumor types will increase Oncophage' s commercial potential
      • Personalized nature could work in Oncophage' s favor
      • Lack of cost effectiveness, clinical benefit and marketing experience will pose significant strategic challenges for Antigenics
  • Forecasts
• CHAPTER 8 DENDRITIC CELL CANCER VACCINES ANALYSIS & FORECASTS
  • Pipeline overview
  • Dendreon' s Provenge (Sipuleucel-T; APC-8015)
    • Drug profile
    • Clinical trial data
      • First Phase III trial failed to meet primary endpoints, although increase in overall survival was demonstrated
      • Second Phase III clinical trial targets patient cohort most likely to derive clinical benefit
      • Phase II results suggest synergy between Provenge and Genentech/Roche' s Avastin
      • Provenge may ultimately need to be compared with Taxotere if it is to expand its use in the HRPC market
      • Provenge may need to tackle the impact of its probable high cost, complex manufacture and potential competition in the HRPC market
      • Provenge' s commercial potential could be enhanced with the backing of an established oncology player
  • Forecasts
• APPENDIX A
  • List of tables
  • List of figures
  • Methodology
    • Datamonitor forecast methodology
    • Datamonitor drug assessment summary
  • Abbreviations
  • Contributing experts
  • Key opinion leader interview transcripts
  • Bibliography
• APPENDIX B
  • About the Oncology analysis team
  • Disclaimer
  • List of Tables
    • Table 1: Late-phase pipeline therapeutic cancer vaccines sales forecasts for the seven major markets ($m), 2006-2015
    • Table 2: Datamonitor drug assessment summary for late-phase pipeline cancer vaccine therapies, 2006
    • Table 3: Therapeutic cancer vaccines in late-phase development, 2006
    • Table 4: Therapeutic cancer vaccines in Phase II development, 2006
    • Table 5: Therapeutic cancer vaccines in Phase I development, 2006
    • Table 6: Pipeline therapeutic cancer vaccines by developmental phase & class, 2006
    • Table 7: Proportion of personalized versus generalized cancer vaccines by phase, 2006
    • Table 8: Pipeline therapeutic cancer vaccines by indication, 2006
    • Table 9: Companies/Institutes with two or more vaccines in the pipeline, 2006
    • Table 10: Memorial Sloan-Kettering Cancer Center' s cancer vaccine therapies portfolio, 2006
    • Table 11: Therion Biologics' cancer vaccine therapies portfolio, 2006
    • Table 12: Common mutations involved in tumor development
    • Table 13: Forecast incidence of cancer across the seven major markets, 2005-2013
    • Table 14: Three main categories of cancer vaccines exist
    • Table 15: Advantages of peptide-based vaccines, 2006
    • Table 16: Advantages and disadvantages of cancer vaccines
    • Table 17: Relative efficacy merits of cancer vaccines
    • Table 18: Relative formulation merits of cancer vaccines
    • Table 19: Types of immune adjuvants
    • Table 20: Late-phase pipeline antigen-specific cancer vaccines, 2006
    • Table 21: Phase II pipeline antigen-specific cancer vaccines, 2006
    • Table 22: Phase I pipeline antigen-specific cancer vaccines, 2006
    • Table 23: Ongoing clinical trial involving Amolimogene, 2006
    • Table 24: Ongoing clinical trial involving GV1001, 2006
    • Table 25: Ongoing clinical trial involving MDX-1379, 2006
    • Table 26: Phase II initial data for MDX-1379 in melanoma
    • Table 27: Ongoing clinical trials involving TroVax, 2006
    • Table 28: Interim Phase II results of TroVax in CRC
    • Table 29: Ongoing clinical trials involving BIOVAXID, 2006
    • Table 30: Ongoing clinical trials involving FavId, 2006
    • Table 31: Interim results of FavId monotherapy Phase III trial in fNHL: Response to Rituxan, December 2006
    • Table 32: Ongoing clinical trial involving MyVax, 2006
    • Table 33: Phase II interim results of MyVax in MCL and DLBCL NHL patients, 1 of 2
    • Table 34: Phase II interim results of MyVax in MCL and DLBCL NHL patients, 2 of 2
    • Table 35: Comparisons of the late-phase anti-idiotype vaccines
    • Table 36: Forecasting assumptions for late-phase antigen-specific cancer vaccines, 2006 (1 of 3)
    • Table 37: Forecasting assumptions for late-phase antigen-specific cancer vaccines, 2006 (2 of 3)
    • Table 38: Forecasting assumptions for late-phase antigen-specific cancer vaccines, 2006 (3 of 3)
    • Table 39: Antigen-specific cancer vaccines sales forecasts, 2006-2015 ($m)
    • Table 40: Research/clinical and commercial attractiveness of the pipeline antigen-specific cancer vaccines, 2006 (1 of 2)
    • Table 41: Research/clinical and commercial attractiveness of the pipeline antigen-specific cancer vaccines, 2006 (2 of 2)
    • Table 42: Late-phase pipeline polyvalent cancer vaccines, 2006
    • Table 43: Phase II pipeline antigen-specific cancer vaccines, 2006
    • Table 44: Phase I pipeline antigen-specific cancer vaccines, 2006
    • Table 45: Ongoing clinical trials involving M-Vax, 2006
    • Table 46: Ongoing clinical trials involving GVAX, 2006
    • Table 47: Ongoing clinical trial involving OncoVAX, 2006
    • Table 48: Ongoing clinical trial involving Oncophage, 2006
    • Table 49: Final Phase III results for Oncophage in stage IV melanoma
    • Table 50: Staging system for stage IV melanoma
    • Table 51: Forecasting assumptions for late-phase polyvalent cancer vaccines, 2006
    • Table 52: Polyvalent cancer vaccines sales forecasts ($m), 2006-2015
    • Table 53: Research/clinical and commercial attractiveness of the pipeline polyvalent cancer vaccines, 2006
    • Table 54: Pipeline dendritic cell cancer vaccines in clinical trials, 2006
    • Table 55: Ongoing clinical trials involving Provenge, 2006
    • Table 56: Three-year final survival analysis for Phase III D9901 Provenge study
    • Table 57: Three-year final survival analysis for Phase III D9902A Provenge study
    • Table 58: Integrated data from D9901/D9902A trials for patients treated with Provenge followed by Taxotere, 1 of 2
    • Table 59: Integrated data from D9901/D9902A trials for patients treated with Provenge followed by Taxotere, 2 of 2
    • Table 60: Forecasting assumptions for Provenge, 2006
    • Table 61: Provenge sales forecasts, 2006-2015 ($m)
    • Table 62: Research/clinical and commercial attractiveness of Provenge, 2006
    • Table 63: Datamonitor drug assessment parameters
    • Table 64: Abbreviations used in Pipeline Insight: Therapeutic Cancer Vaccines (1 of 2)
    • Table 65: Abbreviations used in Pipeline Insight: Therapeutic Cancer Vaccines (2 of 2)
  • List of Figures
    • Figure 1: Antigen-specific cancer vaccines sales forecasts ($m), 2006-2015
    • Figure 2: Polyvalent cancer vaccines sales forecasts, 2006-2015 ($m)
    • Figure 3: Provenge sales forecasts, 2006-2015 ($m)
    • Figure 4: Datamonitor drug assessment summary for late-phase pipeline cancer vaccine therapies, 2006
    • Figure 5: Pipeline therapeutic cancer vaccines by developmental phase & class, 2006
    • Figure 6: Pipeline therapeutic cancer vaccines by class, 2006
    • Figure 7: Pipeline therapeutic cancer vaccines by phase, 2006
    • Figure 8: Antigen-specific cancer vaccines by developmental phase, 2006
    • Figure 9: Polyvalent cancer vaccines by developmental phase, 2006
    • Figure 10: Dendritic cell cancer vaccines by developmental phase, 2006
    • Figure 11: Pipeline therapeutic cancer vaccines by technology platform, 2006
    • Figure 12: Proportion of personalized versus generalized cancer vaccines, 2006
    • Figure 13: Proportion of personalized versus generalized cancer vaccines by phase, 2006
    • Figure 14: Pipeline therapeutic cancer vaccines by indication, 2006
    • Figure 15: Proportion of solid tumors versus hematological malignancies, 2006
    • Figure 16: Late-phase pipeline therapeutic cancer vaccines by indication, 2006
    • Figure 17: Pipeline therapeutic cancer vaccines by company, 2006
    • Figure 18: Global oncology sales ($m), 2002-09
    • Figure 19: Oncology pipeline including supportive care, 2006
    • Figure 20: Forecast incidence of cancer across the seven major markets, 2005-2013
    • Figure 21: Combined incidence for breast, lung, prostate and colorectal cancer rises with age in seven major markets, 2003
    • Figure 22: Incidence increases, while the rate of cure and death reduces disease prevalence
    • Figure 23: Point prevalence for colorectal and lung cancer differs markedly despite similar rates of incidence
    • Figure 24: Unmet needs in cancer, 2006
    • Figure 25: To achieve success, cancer vaccines need to overcome immune tolerance
    • Figure 26: Disadvantages associated with cancer vaccines are currently more significant than advantages
    • Figure 27: TeloVac Phase III trial outline, 2006
    • Figure 28: GMK' s mode of action
    • Figure 29: Trial design of Phase II study of FavId in progressive NHL
    • Figure 30: Gernitope' s personalized immunotherapy (MyVax) production system
    • Figure 31: Antigen-specific cancer vaccines sales forecasts ($m), 2006-2015
    • Figure 32: Research/clinical and commercial attractiveness of pipeline antigen-specific cancer vaccines, 2006
    • Figure 33: Polyvalent cancer vaccines sales forecasts, 2006-2015 ($m)
    • Figure 34: Research/clinical and commercial attractiveness of the pipeline polyvalent cancer vaccines, 2006
    • Figure 35: Provenge sales forecasts, 2006-2015 ($m)
    • Figure 36: Research/clinical and commercial attractiveness of Provenge, 2006