2013年之前的癌症疫苗開發動向

The launch of Sanofi Pasteur MSD' s Gardasil and GSK' s Cervarix has propelled cancer vaccines from research obscurity to a key area of commercial and clinical interest. But can the sector capitalise on these gains and really fulfil its promise?

By 2010, the global cancer market is expected to generate sales in excess of US$60 billion due to growth in the sales of existing innovative products and the launch of nearly 60 new products which will account for around 30% of total drug launches.

But where do cancer vaccines fit into this outlook? At present, prophylactic vaccines dominate the cancer vaccine sector following the recent launches of Sanofi Pasteur MSD' s Gardasil and GlaxoSmithKline' s Cervarix. We expect that sales of these vaccines will break through US$4 billion by 2011. While there is no therapeutic vaccine market, so to speak of, at present, it has the potential to mirror the growth seen in the monoclonal antibody market, and reach sales in excess of US$5 billion by 2012. This prediction may be optimistic and is highly dependent on vaccines being approved for major cancer indications - no small challenge taking the development history of the sector.

While no new therapeutic cancer vaccine has been approved recently the product pipeline has changed substantially, shifting from one filled with vaccines at the Phase I and II stage, to a more mature pipeline reflecting a shift in development towards the later stages. This is a consequence, not only of the age of the pipeline, but of the difficulties and pitfalls that therapeutic cancer vaccine development faces. Many vaccines have fallen by the wayside for one reason or another. Indeed the rush to join this area of research has waned slightly with the realisation that products are harder to bring to market than first anticipated.

Cancer vaccine research is coming to fruition, with a number of products now in Phase III trials and 15 therapeutic cancer vaccines realistically expected to launch by 2013

Despite the challenges faced by the sector, we predict that by 2010, there will be six new therapeutic cancer vaccine approvals, led by Favrille' s FavId for B-cell non-Hodgkin' s lymphoma. This number looks set to increase quickly with the possibility of 21 vaccines being launched by the end of 2013, although 15 seems a more realistic scenario given the historic failure rate for therapeutic cancer vaccines in Phase III development. These products look set to target some of the "big" cancers, with launches for vaccines against renal cell carcinoma, melanoma, prostate, non-small cell lung and colorectal cancer.

But there are many challenges ahead

It is still not clear how best to use cancer vaccines with respect to disease stage and in combination with other therapies. How should clinical trials be designed so that the endpoints reflect the actions of the vaccines? It looks likely that when therapeutic cancer vaccines finally make their way on to the market and into clinical use it will be alongside current therapies as part of combination regimens that keep cancer in check. The current vaccines in development do not seem to be the "magic bullet" for cancer that many had hoped they would be. Instead they look set to occupy a much needed place in the growing choice of treatments that are needed to keep cancer under control.

The problems faced by the sector are illustrated by Dendreon' s Provenge. Everything was right: a biotech company getting a vaccine approved for a major indication in a large market. However, this was not to be, as the FDA ruled that additional survival data was needed, signalling another setback for a sector that has seen its fair share of failures and false dawns.

But it was also a timely reminder for developers that the path to market for therapeutic cancer vaccines is not going to be an easy one. Companies must now focus on conducting well-designed trials with achievable but robust endpoints in suitable patient populations, and perhaps even consider combination trials with other therapies.

Who are the players and products in the race to launch? This report critically assesses the candidates in their wider market context

This insightful and data-rich management report Cancer Vaccine Developments to 2013, fully evaluates the products and their developers. In more than 180 pages, the report provides a complete review of the market and its likely development to 2013.

Cancers covered

• Brain
• Breast
• Gastrointestinal
• Genito-urinary
• Gynaecological
• Haematological
• Lung
• Melanoma/Sarcoma

Types of cancer vaccine

• Antigen/adjuvant vaccines
• Whole-cell tumour vaccines
• Dendritic cell vaccines
• Viral vectors and DNA vaccines
• Idiotype vaccines

The report answers key questions...

• Who' s developing what, and with whom?
• What are the prospects for Gardasil achieving US$1.6 billion sales by 2011?
• Which products are likely to launch in 2009 and 2010?
• Why do some cancer vaccines fail?
• Which company is leading the race to develop a breast cancer vaccine?
• What cancer vaccines are there in Phase II/III for lung, breast, prostate and colorectal cancer?
• What unique regulatory hurdles must cancer vaccines overcome?

Incorporating information from Espicom' s extensive cancer databases, case studies and direct contact with developers, the report provides unique insight, forecasts, product launch predictions and much, much more. Essential reading for investors, developers and industry professionals!

• EXECUTIVE SUMMARY
• INTRODUCTION
  • What is a cancer vaccine?
    • Figure 1. Potential advantages of therapeutic vaccines for cancer
  • Prophylactic vaccines
    • Overview
      • Table 1. Infectious agents involved in cancer
    • Limitations
  • Therapeutic vaccines
    • Overview
      • Figure 2. Vaccines in Phase II/III development by vaccine type
    • Ag/adjuvant vaccines
    • Whole cell tumour vaccines
    • Dendritic cell vaccines
    • Viral vectors and DNA vaccines
      • DNA vaccines
      • Vector-based vaccines
    • Idiotype vaccines
  • Antigens
    • Carcinoembryonic antigen
    • Ganglioside molecules
    • Heat shock proteins
    • MART-1
    • MUC1
    • NY-ESO-1
    • Prostate specific antigen
    • Sialyl Tn
    • Telomerase
    • Tyrosinase
  • Adjuvants
    • AS04
    • Bacillus Calmette Guerin
    • Interleukins
    • Granulocyte monocyte-colony stimulating factor
    • Incomplete Freund' s adjuvant
    • Keyhole limpet hemocyanin
    • Montanide ISA-51
    • QS-21
  • Monitoring the immune response
    • Proliferation
    • Peptide-major histocompatibility complex multimers
    • ELIS pot
    • Intracellular cytokine assays
  • Challenges of developing vaccines
    • General challenges
      • Antigen selection
      • Adjuvants
      • Generating the correct immune response
      • Long-term immune memory
    • Cancer-vaccine specific challenges
      • Function of thymus
      • Heterogeneity in immune responses
      • Evasion of immune system
      • Tumour-induced immunosuppression
      • Induction of autoimmunity
    • Product standardisation and characterisation
• MARKET FUTURE
  • Potential targets
    • Tumour types
      • Figure 3. Vaccines in Phase II/III development by indication
    • Disease incidence
      • Figure 4. US cancer statistics
    • Disease settings
  • Combination therapy
    • Figure 5. Potential combination therapy with cancer vaccines
  • Clinical trial designs
    • Proposed clinical trial design
      • Table 2. Proposed clinical trial designs for cancer vaccines
    • Endpoints
      • Patient selection
      • Survival
      • Other time-to-event endpoints
      • Response rate
      • Endpoint modifications
      • Patient-reported outcomes and quality-of-life endpoints
      • Biologic markers
    • Regulatory challenges
    • Market leaders
      • Figure 6. Vaccines in Phase II/III development by company
      • Figure 7. Factors faced by vaccines from their competitors
    • Cost effectiveness
    • Market growth
      • Potential market size
        • Figure 8. Growth drivers and resistors in the therapeutic cancer vaccine market
      • Competition
    • Cervical cancer vaccines: novel challenges
      • Figure 9. Issues faced by human papillomavirus vaccines
    • HPV vaccines
      • Gardasil
      • Cervarix
    • Vaccination population
      • Australia
      • Canada
      • Europe
        • Belgium
        • France
        • Switzerland
      • US
    • Vaccine cost
      • US Government immunisation schemes
    • European reimbursement
      • Sweden
      • UK
  • Less developed countries
  • Safety issues
  • Screening
  • Future research
• MAJOR AGREEMENTS
  • The advantage of collaboration
    • Figure 10. The benefits of collaboration
    • Table 3. Agreements that could shape the cancer vaccine market
  • The Biomira and Merck KGaA story
    • Stimuvax
  • The Geron and Merck & Co story
    • GRNVAC 1
  • The GSK and Ludwig Institute for Cancer Research story
    • MA GE-A3
  • The Oxford BioMedica and sanofi-aventis story
    • TroVax
  • The Roche and Transgene story
    • TG4001
  • Terminated agreements: big pharma burns its fingers
    • Table 4. Terminated agreements between biotech companies and big pharma
  • Canvaxin
    • CancerVax and Serono
      • The agreement
      • Why did the agreement end?
  • Melacine
    • Corixa and Schering-Plough
      • The agreement
      • Why did the agreement end?
  • GMK Vaccine
    • Progenics Pharmaceuticals and Bristol-Myers Squibb
      • The agreement
      • Why did the agreement end?
  • Insegia
    • Aphton and sanofi pasteur
      • The agreement
      • Why did the agreement end?
    • Theratope
      • Biomira and Merck KGaA
        • The agreement
        • Why did the agreement end?
• FAILED CANCER VACCINES
  • Figure 11. Reasons why cancer vaccines may have failed in clinical trials
  • Cancer vaccines that have failed in Phase II /II development
    • Table 5. Major cancer vaccine failures
  • Canvaxin failure leads to CancerVax merger
    • Product history
    • Why did the vaccine fail?
  • GMK Vaccine loses BMS backing following inferior results
    • Product history
    • Why did the vaccine fail?
  • GVAX highlights limits of patient-specific vaccines
    • Product history
    • Why did the vaccine fail?
  • Insegia problems force Aphton' s bankruptcy
    • Product history
    • Why did the vaccine fail?
      • Table 6. Insegia Phase III results showing survival by Ab response
  • Melacine; launched and disappeared
    • Product history
    • Why did the vaccine fail?
  • PANVAC-VF failure forces liquidation of Therion
    • Product history
    • Why did the vaccine fail?
  • Early Reniale data still waiting for confirmation
    • Product history
    • Why did the vaccine fail?
  • Theratope disappointment wards off Merck
    • Product history
    • Why did the vaccine fail?
• LAUNCHED PRODUCTS
  • Vaccines currently on the market
    • Table 7. Vaccines currently on the market
  • OncoVAX
    • Intracel
    • The market(s)
    • The technology
    • Results to date
  • M-Vax
    • AVAX Technologies
      • The market(s)
      • The technology
      • Results to date
  • Gardasil
    • Sanofi Pasteur MSD
      • The market(s)
      • The technology
      • Results to date
  • Cervarix
    • GlaxoSmithKline
      • The market(s)
      • The technology
      • Results to date
  • Estimated sales
    • Gardasil
      • Sanofi Pasteur MSD (sanofi-aventis' joint venture with Merck & Co)
        • Sales forecasts and assumptions
        • Table 8. Sales forecast for Gardasil
    • Cervarix
      • GlaxoSmithKline
      • Sales forecasts and assumptions
        • Table 9. Sales forecast for Cervarix
• VACCINES IN DEVELOPMENT
  • Table 10. Who' s developing what in Phase II/III?
  • Key launches
    • Table 11. Key vaccine launches to 2013
    • Figure 12. Key vaccine launches by indication
    • Figure 13. Key vaccine launches by vaccine type
• BREAST CANCER
  • Overview
    • Figure 14. Development phase breakdown for breast cancer
    • Figure 15. Vaccine type breakdown for breast cancer
  • Why is vaccine therapy being explored for breast cancer?
  • Vaccines in Phase II development
    • Table 12. Vaccines in Phase II development for breast cancer
  • Vaccines in Phase I development
    • Table 13. Vaccines in Phase I development for breast cancer
  • Vaccines of interest
    • AE37
    • dHER2 vaccine
    • NeuVax
• HAEMATOLOGICAL CANCER
  • Overview
    • Figure 16. Development phase breakdown for haematological cancer
    • Figure 17. Vaccine type breakdown for haematological cancer
  • Why is vaccine therapy being explored for non-Hodgkin' s lymphoma?
  • Why is vaccine therapy being explored for leukaemia?
  • Vaccines in Phase III development
    • Table 14. Vaccines in Phase III development for haematological cancers
  • Vaccines in Phase II development
    • Table 15. Vaccines in Phase II development for haematological cancers
  • Vaccines in Phase I development
    • Table 16. Vaccines in Phase I development for haematological cancers
  • BiovaxID
  • Biovest International (Accentia Biopharmaceuticals)
    • The technology
      • Figure 18. The process involved in manufacturing BiovaxID
    • Pivotal trial
    • Other important trials
    • Results to date
    • Next major event/milestone
    • Agreements
    • Market size
    • Competitors
    • Analysis
      • Strengths
      • Weaknesses
  • FavId
    • Favrille
      • The technology
        • Figure 19. The process involved in manufacturing FavId
    • Pivotal trial
    • Other important trials
    • Results to date
    • Next major event/milestone
    • Agreements
    • Market size
    • Competitors
    • Analysis
      • Strengths
      • Weaknesses
  • MyVax
    • Genitope
      • The technology
        • Figure 20. The process involved in manufacturing MyVax
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
  • PR1 vaccine
    • The Vaccine Company
      • The technology
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
  • Other vaccines of interest
    • Oncophage
• LUNG CANCER
  • Overview
    • Figure 21. Development phase breakdown for lung cancer
    • Figure 22. Vaccine type breakdown for lung cancer
  • Why is vaccine therapy being explored for lung cancer?
  • Vaccines in Phase II development
    • Table 17. Vaccines in Phase III development for lung cancer
  • Vaccines in Phase II development
    • Table 18. Vaccines in Phase II development for lung cancer
  • Vaccines in Phase I development
    • Table 19. Vaccines in Phase I development for lung cancer
  • Lucanix
    • NovaRx
      • The technology
    • Pivotal trial
    • Other important trials
    • Results to date
    • Next major event/milestone
    • Agreements
    • Market size
    • Competitors
    • Analysis
      • Strengths
      • Weaknesses
• MAGE-A3
  • GlaxoSmithKline
    • The technology
    • Pivotal trial
    • Other important trials
    • Results to date
    • Next major event/milestone
    • Agreements
    • Market size
    • Competitors
    • Analysis
      • Strengths
      • Weaknesses
  • Stimuvax
    • Biomira/Merck KGaA
      • The technology
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Agreements
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
  • Other vaccines of interest
    • IDM -2101
    • IN GN 225
• GENITO-URINARY CANCER
  • Overview
    • Figure 23. Development phase breakdown for genito-urinary cancer
    • Figure 24. Vaccine type breakdown for genito-urinary cancer
  • Why is vaccine therapy being explored for prostate cancer?
  • Why is vaccine therapy being explored for renal cell carcinoma?
  • Vaccines in Phase II development
    • Table 20. Vaccines in Phase III development for genito-urinary cancers
  • Vaccines in Phase II development
    • Table 21. Vaccines in Phase II development for genito-urinary cancers
  • Vaccines in Phase I development
  • Table 22. Vaccines in Phase I development for genito-urinary cancers
• DCVax-Prostate
  • Northwest Biotherapeutics
    • The technology
    • Pivotal trial
    • Other important trials
    • Results to date
    • Next major event/milestone
    • Market size
    • Competitors
    • Analysis
      • Strengths
      • Weaknesses
  • GVAX vaccine
    • Cell Genesys
      • The technology
      • Pivotal trials
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Agreements
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
  • Oncophage
    • Antigenics
      • The technology
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
• Provenge
  • Dendreon
    • The technology
    • Pivotal trial
    • Other important trials
    • Results to date
    • Next major event/milestone
    • Market size
    • Competitors
    • Analysis
      • Strengths
      • Weaknesses
  • TroVax
    • Oxford BioMedica/sanofi-aventis
      • The technology
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Agreements
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
    • Other vaccines of interest
      • GRNVAC 1
      • Onyvax-P
      • Reniale
• GYNAECOLOGICAL CANCER
  • Overview
    • Figure 25. Development phase breakdown for gynaecological cancer
    • Figure 26. Vaccine type breakdown for gynaecological cancer
  • Why is vaccine therapy being explored for ovarian cancer?
  • Vaccines in Phase II development
    • Table 23. Vaccines in Phase III development for gynaecological cancers
  • Vaccines in Phase II development
    • Table 24. Vaccines in Phase II development for gynaecological cancers
  • Vaccines in Phase I development
    • Table 25. Vaccines in Phase I development for gynaecological cancers
  • Amolimogene
    • MGI Pharma
      • The technology
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
  • TG4001
    • Transgene/Roche
      • The technology
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Agreements
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
    • Other vaccines of interest
      • CV ac
      • HspE7
• GASTROINTESTINAL CANCER
  • Overview
    • Figure 27. Development phase breakdown for gastrointestinal cancer
    • Figure 28. Vaccine type breakdown for gastrointestinal cancer
  • Why is vaccine therapy being explored for pancreatic cancer?
  • Why is vaccine therapy being explored for colorectal cancer?
  • Vaccines in Phase III development
    • Table 26. Vaccines in Phase III development for gastrointestinal cancers
  • Vaccines in Phase II development
    • Table 27. Vaccines in Phase II development for gastrointestinal cancers
  • Vaccines in Phase I development
    • Table 28. Vaccines in Phase I development for gastrointestinal cancers
  • GV1001
    • Pharmexa
      • The technology
      • Pivotal trials
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
  • OncoVAX
    • Intracel
      • The technology
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
  • TroVax
    • Oxford BioMedica/sanofi-aventis
      • The technology
      • Other important trials
      • Results to date
        • Phase II results of TroVax plus CT in CRC
        • Phase II results of TroVax adjuvant therapy in CRC
      • Next major event/milestone
      • Agreements
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
    • Other vaccines of interest
      • Avicine
      • Gastrimmune
      • Oncophage
• BRAIN CANCER
  • Overview
    • Figure 29. Development phase breakdown for brain cancer
    • Figure 30. Vaccine type breakdown for brain cancer
  • Why is vaccine therapy being explored for brain cancer?
  • Vaccines in Phase II development
    • Table 29. Vaccines in Phase II development for brain cancer
  • Vaccines in Phase I development
    • Table 30. Vaccines in Phase I development for brain cancer
  • CDX-110
    • Celldex Therapeutics
      • The technology
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
  • DCVax-Brain
  • Northwest Biotherapeutics
    • The technology
    • Pivotal trial
    • Other important trials
    • Results to date
    • Next major event/milestone
    • Market size
    • Competitors
    • Analysis
      • Strengths
      • Weaknesses
  • Other vaccines of interest
    • Oncophage
• MELANOMA/SARCOMA
  • Overview
    • Figure 31. Development phase breakdown for melanoma/sarcoma
    • Figure 32. Vaccine type breakdown for melanoma/sarcoma
  • Why is vaccine therapy being explored for melanoma?
  • Vaccines in Phase II development
    • Table 31. Vaccines in Phase III development for melanoma/sarcoma
  • Vaccines in Phase II development
    • Table 32. Vaccines in Phase II development for melanoma/sarcoma
  • Vaccines in Phase I development
    • Table 33. Vaccines in Phase I development for melanoma/sarcoma
  • Allovectin-7
    • Vical
      • The technology
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Agreements
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
  • MDX-1379
    • Medarex/Bristol-Myers Squibb
      • The technology
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Agreements
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
  • M-Vax
    • AVAX Technologies
      • The technology
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
  • Oncophage
    • Antigenics
      • The technology
      • Pivotal trial
      • Other important trials
      • Results to date
      • Next major event/milestone
      • Market size
      • Competitors
      • Analysis
        • Strengths
        • Weaknesses
  • Other vaccines of interest
    • Uvidem
• OTHER VACCINES
  • Overview
    • Vaccines in Phase II development
      • Table 34. Vaccines in Phase II development for other cancers
  • Vaccines in Phase I development
    • Table 35. Vaccines in Phase I development for other cancers
• SOURCES
  • Espicom sources
  • Others