Pipeline Insight: Cancer Vaccines and Cell Therapies
Scope
Report Highlights
Reasons to Purchase
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE - page 2
- About the Oncology pharmaceutical analysis team - page 2
- Richard Faint - Director of Oncology - page 2
- About the Oncology pharmaceutical analysis team - page 2
- CHAPTER 1 EXECUTIVE SUMMARY - page 3
- Datamonitor insight into the cancer vaccines market - page 3
- CHAPTER 2 PIPELINE OVERVIEW & FUTURE FOCUS - page 18
- Pipeline overview - page 18
- Antigen-specific vaccines are the major focus of development - page 26
- Antigen-specific vaccines constitute over half of the current cancer vaccine pipeline - page 26
- High specificity and lower complexity of manufacture increase popularity of antigen-specific vaccine approaches - page 27
- Cell-based vaccines allow for the inclusion of a wide range of antigens, but present significant manufacturing, sterility and cost issues - page 28
- Antigen-specific vaccines constitute over half of the current cancer vaccine pipeline - page 26
- Potential commercial rewards dictate tumor focus - page 29
- 'Big four' tumor types remain popular indications, joined by immunologically driven malignancies, such as melanoma and renal cell carcinoma - page 29
- As expected, the 'big four' tumor types feature heavily in the current cancer vaccine pipeline - page 30
- Spontaneous tumor remissions and documented responses to cytokines in melanoma and renal cell carcinoma support employment of an immunotherapeutic approach - page 30
- In adopting a novel approach to tumor immunotherapy the high unmet needs of pancreatic cancer may be overcome - page 31
- Hematological malignancies are perhaps the ideal target for cancer vaccines due to facilitated infiltration of T-cells - page 31
- Cervical cancer and head & neck cancer are ideal candidates for the development of prophylactic vaccines - page 32
- Cancer vaccines for remaining indications exploit commonly overexpressed tumor-associated antigens or the potential of dendritic cells - page 32
- As anticipated, the majority of the pipeline is made up of generalized rather than personalized cancer vaccines - page 32
- Generalized cancer vaccines represent three quarters of the pipeline - page 33
- 'Big four' tumor types remain popular indications, joined by immunologically driven malignancies, such as melanoma and renal cell carcinoma - page 29
- Fragmentation of the cancer vaccine market means strategic partnerships with major oncology players will ease the path to commercialization - page 34
- At least 64 companies are involved in the clinical development of cancer vaccines, 80% of which are small biotechnology firms - page 34
- Companies with multiple cancer vaccine candidates have relatively immature portfolios, therefore opportunity for commercial success cannot be based on pipeline volume alone - page 35
- Several companies are supported by strong strategic partnerships - page 36
- CSL/UniQuest Ltd, Medarex, MedImmune and Therion Biologics - key players in the cancer vaccine market - page 38
- Key metrics - page 39
- Datamonitor pipeline assessment summary - page 42
- Future focus - cancer vaccines face many challenges on route to approval - page 45
- CHAPTER 3 PIPELINE DYNAMICS - page 49
- A diverse range of disease subtypes - page 49
- Genetic basis of cancer evolution - page 49
- Tumorigenesis is the result of cooperative accumulated mutations - page 50
- Existing pharmacotherapy approaches provide limited treatment benefit - page 51
- Cytotoxic drugs lack specificity - page 51
- Hormonal or endocrine therapy provides incremental benefit in selected tumors - page 52
- Optimizing current treatment strategies is paramount - page 52
- The emergence of targeted treatment heralds a revolution in cancer pharmacotherapy - page 52
- Dynamic cancer market offers significant commercial opportunity - page 53
- Ongoing sales growth drives the market - page 53
- Intensive R&D produces a rich developmental pipeline - page 53
- Growing patient population and significant unmet needs propel innovation in the cancer market - page 54
- Cancer epidemiology - an expanding patient base - page 54
- Significant areas of unmet need persist - page 59
- Clinical and strategic threats to the commercialization of cancer drugs - page 62
- Progressively rising R&D costs threaten industry productivity - page 62
- High attrition rates can be mitigated by improved strategic decision-making - page 62
- Lengthening drug approval process a consequence of increased regulatory demands - page 63
- Pharmacoeconomic pressures drive payers to implement restrictive pricing and reimbursement policies - page 63
- Increased therapeutic and generic competition results in reduced periods of market exclusivity - page 64
- Segmentation of market will require changes in clinical trial methodology - page 65
- Progressively rising R&D costs threaten industry productivity - page 62
- CHAPTER 4 CANCER VACCINES & CELL THERAPIES OVERVIEW - page 66
- The goal: active, specific immunotherapy - page 66
- Skepticism surrounds the history and future commercial viability of this technology - page 67
- Overcoming immune tolerance is the key to success - page 67
- Classification of pipeline products - page 69
- Polyvalent vaccines - page 70
- Whole-cell vaccines - page 70
- Tumor lysate vaccines - page 70
- Shed antigens - page 71
- Heat-shock proteins - page 71
- Antigen-specific vaccines - page 71
- Tumor-associated antigen - carbohydrate - page 71
- Tumor-associated antigen - recombinant protein - page 72
- Peptide-based vaccine - page 72
- Recombinant virus vaccine - page 72
- Anti-idiotype vaccine - page 73
- DNA vaccine - page 73
- Dendritic cell vaccines - page 74
- Prophylactic vaccines - page 75
- Polyvalent vaccines - page 70
- Relative merits of different cancer vaccine approaches show no clear market leader - page 75
- CHAPTER 5 NEW MARKET, NEW ISSUES - page 77
- Lack of precedent confers unique strategic challenges - page 77
- Regulatory issues cloud the road to commercialization - page 78
- FDA request for further clinical data led to cessation of Corixa's US development of Melacine - page 78
- Formulation and manufacturing concerns raised by regulatory bodies - page 79
- M-Vax's route to market hampered due to manufacturing and formulation considerations - page 79
- Skepticism over cost-effectiveness hampers commercialization - page 80
- Expense of manufacture may hamper the widespread uptake of Intracel's OncoVAX - page 80
- Prophylactic vaccines have demonstrable clinical benefit - page 81
- Prophylactic BCG vaccines are gold standard for bladder cancer - page 81
- Wide range of indications under development makes it difficult to compare efficacies of each class of cancer vaccine - page 82
- Datamonitor research has shown pipeline cancer vaccines to be in development for at least 17 tumor types - page 82
- Regulatory issues cloud the road to commercialization - page 78
- Changing the paradigm in clinical trial design - page 83
- Clinical trial endpoints are starting to evolve to accommodate changing needs - page 83
- Multiple clinical trial endpoints are required to gain complete overview of a drug's therapeutic potential - page 83
- Composite endpoints and patient selection can significantly alter clinical trial outcomes in light of the evolving oncology market - page 83
- Investigators must establish and consistently employ standard response criteria specific to the assessment of cancer vaccines - page 84
- Standard response criteria may have become somewhat redundant - page 84
- Lack of adequate controls in the design of randomized clinical trials - page 85
- Immune monitoring should be integral to assessing the efficacy of vaccine strategies - page 86
- Increasing evidence shows that immune monitoring may constitute a viable clinical trial endpoint in cancer vaccine development - page 86
- Clinical trial endpoints are starting to evolve to accommodate changing needs - page 83
- Optimizing cancer vaccine delivery strategies - page 87
- Cancer vaccines are likely to be most efficacious in the setting of minimal residual disease - page 87
- Tumor response is more likely in the adjuvant setting, yet clinical trials continue to focus on metastatic patients - page 87
- Timing of vaccine delivery is crucial if part of multi-modality regimen - page 89
- Immunosuppressive therapy can compromise the efficacy of cancer vaccines - page 89
- Strategies to overcome the influence of neutralizing antibodies following vaccine administration - page 90
- Multiple vaccinations induce development of strong neutralizing antibodies that leave subsequent administration futile - page 90
- Cancer vaccines are likely to be most efficacious in the setting of minimal residual disease - page 87
- Significant hurdles challenge the path to commercialization - page 90
- Lack of precedent confers unique strategic challenges - page 77
- CHAPTER 6 POLYVALENT VACCINES DRUG ANALYSIS & FORECASTS - page 92
- In comparison to autologous vaccines, allogeneic approaches are likely to realize an expedited path to commercialization - page 92
- Pipeline overview - page 92
- Cell Genesys's GVAX counters the belief that there is no dose-related effect with cancer vaccines - page 93
- First-generation GVAX demonstrates survival benefit in Phase II clinical trials - page 93
- Re-engineered second-generation GVAX confers increased potency, as confirmed by second round of Phase II clinical trials - page 94
- Ongoing Phase III clinical trials need to confirm benefits of GVAX's increased potency - page 94
- Existing manufacturing infrastructure and potential clinical viability of GVAX make Cell Genesys a leading player in the race to commercialization - page 95
- Cell Genesys will require an expansion of its marketing and distribution resources to optimize GVAX's commercialization - page 95
- CancerVax/Serono's Canvaxin - despite FDA action hampering developmental partnership increases first-to-market potential - page 96
- Phase II clinical trials demonstrate promising survival benefits - page 96
- Results from Phase III trial anticipated by late 2005/early 2006, despite temporary FDA suspension of study - page 97
- Canvaxin's formulation allows achievable economies of scale - page 97
- Melanoma patients have limited treatment options, so an effective vaccine is likely to enjoy significant uptake - page 98
- CancerVax's partnership with Serono bolsters Canvaxin's first-to-market potential - page 98
- Antigenics's Oncophage - early-stage trials have demonstrated limited clinical benefit - page 98
- Improved second-generation formulation facilitates use in early-stage disease - page 99
- Phase II trials have demonstrated limited clinical benefit in renal cell carcinoma - page 99
- Promising early evidence of immune activity shown in melanoma - page 100
- NHL as an appropriate tumor target expands commercial potential - page 100
- Personalized nature could work in Oncophage's favor although the regulatory and logistical issues that cloud the commercialization of these vaccines prevail - page 101
- Lack of cost-effectiveness, clinical benefit and marketing experience will pose significant strategic challenges for Antigenics - page 101
- Forecasts - page 102
- Datamonitor drug assessment summary - page 104
- In comparison to autologous vaccines, allogeneic approaches are likely to realize an expedited path to commercialization - page 92
- CHAPTER 7 ANTIGEN-SPECIFIC VACCINES DRUG ANALYSIS & FORECASTS - page 106
- High rate of clinical failure associated with antigen-specific vaccines in late-stage development - page 106
- Pipeline overview - page 106
- Aphton/Sanofi-Aventis's Insegia (G17DT) fails to meet primary endpoint in Phase III pancreatic cancer study - page 109
- Combination of Insegia and Gemzar fails to meet primary endpoints in Phase III clinical trial for pancreatic cancer - page 110
- Insegia monotherapy shows benefit in pancreatic cancer patients unable to receive chemotherapy - page 110
- If Phase II benefits in gastric cancer are replicated in a Phase III study, commercial potential of Insegia will be enhanced - page 111
- Aphton's partnership with Sanofi-Aventis will help drive Insegia's market uptake following regulatory approval - page 111
- Biomira's Theratope - failed Phase III study casts doubt over commercial viability - page 112
- Breast cancer Phase III clinical trial fails to meet primary endpoints - page 112
- Phase II study provides basis for continued development in colorectal cancer - page 113
- Biomira would benefit from collaboration with a developmental partner - page 113
- Progenics' GMK - despite relevance of antigen, Phase III trials have failed to demonstrate clinical benefit - page 114
- Early-phase results demonstrate GMK's ability to induce an antibody response - page 114
- GMK proven inferior to standard treatment for stage III melanoma, although a separate ongoing Phase II study in the adjuvant setting may garner better results - page 114
- Lack of commercialization experience and marketing partner will affect GMK's potential - page 115
- A superior strategy may be to shift investment to more lucrative opportunities - page 115
- Medarex/Bristol-Myers Squibb's MDX-1379 - evidence of enhanced immune response is accompanied by potentially dose-limiting autoimmunity - page 115
- Autoimmunity induced in Phase II clinical trials proves that MDX-010 and MDX-1379 are heightening the level of immune response - page 116
- If encouraging, results from an ongoing Phase III clinical trial will support a BLA - page 116
- Optimizing the risk-benefit ratio is paramount in progressing commercial development - page 117
- Partnership with Bristol-Myers Squibb will put Medarex at a significant advantage - page 117
- Therion Biologics' PANVAC-VF - validity of antigen targets could offer hope to pancreatic cancer patients - page 118
- Development of PANVAC-VF characterized by promising Phase I results but a notable absence of reported Phase II data - page 118
- Clinical potential of PANVAC-VF remains to be definitively established and would benefit from a collaborative relationship with an well-known oncology player - page 119
- Igeneon's IGN-101 - low awareness of both the company and its lead product candidate present a major hurdle - page 120
- Ongoing Phase III trials target three of the 'big four' tumor types - page 120
- Phase II clinical trials demonstrate vaccine immunogenicity bur show limited survival benefit - page 120
- Aphton's acquisition of Igeneon may help drive development of IGN-101 - page 121
- Favrille's FavID - by targeting patient population with few recognized treatment options, regulatory bar is lowered - page 121
- Phase II clinical trials have shown prolongation of TTP - page 121
- Ongoing Phase III trial needs to confirm clinical benefit and safety profile - page 122
- Favrille's lack of commercial experience will be a barrier to optimizing market penetration - page 122
- Biovest/Accentia's BIOVAXID - companies should strive to exploit potential first-to-market advantage - page 123
- Long-term Phase II study follow-up suggests favorable survival benefits - page 123
- Ongoing Phase III trial was initiated in January 2000, indicating proximity to completion - page 123
- Genitope's MyVax - second-to-market status may be saved by targeting slightly different patient population than BIOVAXID - page 124
- Phase II clinical trials show greater number of immune responses among previously untreated patients - page 124
- Phase III clinical trials approaching completion - page 124
- Despite being a year behind its main competitor, MyVax increases its commercial potential by targeting an earlier stage treatment - page 124
- Vical's Allovectin-7 - another vaccine that confounds the theory of an absence of dose-related effect - page 125
- Phase III studies investigating low-dose Allovectin-7 terminated due to lack of efficacy - page 125
- Phase III trial investigating high-dose Allovectin-7 recently granted clearance following completion of SPA with the FDA - page 125
- Vical intends to seek development partner, which will greatly aid Allovectin-7's prospects for commercialization - page 126
- Results from second Phase III are pivotal to Allovectin's commercial viability - page 126
- Forecasts - page 126
- Datamonitor drug assessment summary - page 130
- High rate of clinical failure associated with antigen-specific vaccines in late-stage development - page 106
- CHAPTER 8 DENDRITIC CELL VACCINES ANALYSIS & FORECASTS - page 134
- Dendreon's Provenge forges the way in the technologically appealing dendritic cell approach - page 134
- Pipeline overview - page 134
- Dendreon's Provenge (APC-8015) - promises to be first to market within this class of vaccines - page 135
- First Phase III trial failed to meet primary endpoints, although increase in overall survival was demonstrated - page 135
- Second Phase III clinical trial targets patient cohort most likely to derive clinical benefit - page 136
- Phase II clinical trial results suggest synergy between Provenge and Genentech/Roche's Avastin - page 136
- Provenge's probable high cost and complex manufacture may be offset by being the first immunotherapeutic to demonstrate a survival benefit in HRPC - page 136
- Provenge's commercial potential could be enhanced with the backing of an established oncology player - page 137
- Forecasts - page 137
- Datamonitor drug assessment summary - page 139
- Dendreon's Provenge forges the way in the technologically appealing dendritic cell approach - page 134
- APPENDIX A - page 142
- List of tables - page 142
- List of figures - page 145
- Methodology - page 147
- Datamonitor forecast methodology - page 147
- Datamonitor drug assessment summary - page 148
- Contributing experts - page 151
- Opinion leader interview transcripts - page 152
- Doctor Vincenzo Cerundolo, Professor of Immunology, Head Cancer Research UK Tumor Immunology Program, Associate Director of MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK - page 152
- Doctor John Grange, Professor, Centre for Infectious Diseases and International Health, Department of Medicine, Royal Free and University College Medical School, London, UK - page 158
- Doctor Elke Jaeger, Medical Oncologist, Department of Oncology, Krankenhaus Nordwest, Frankfurt, Germany - page 166
- Doctor Howard Kaufman, Vice Chairman of Surgical Oncology & Associate Professor of Clinical Surgery, Department of Surgery, Columbia University, New York, US - page 170
- Doctor Philip Livingston, Medical Oncologist, Memorial Sloan-Kettering Cancer Center, New York, US - page 179
- Doctor Daniel Speiser, Associate Member, Division of Clinical Onco-immunology, Ludwig Institute for Cancer Research, Lausanne, Switzerland - page 185
- Bibliography - page 192
- APPENDIX B - page 200
- About Datamonitor - page 200
- About Datamonitor Healthcare - page 200
- Datamonitor Healthcare's therapy area capabilities - page 201
- About the Oncology analysis team - page 202
- Disclaimer - page 203
- About Datamonitor - page 200
- List of Tables
- Table 1: Late-phase cancer vaccines in development, 2005 (1 of 2) - page 18
- Table 2: Late-phase cancer vaccines in development, 2005 (2 of 2) - page 19
- Table 3: Phase II cancer vaccines in development, 2005 (1 of 2) - page 20
- Table 4: Phase II cancer vaccines in development, 2005 (2 of 2) - page 21
- Table 5: Phase I cancer vaccines in development, 2005 (1 of 4) - page 22
- Table 6: Phase I cancer vaccines in development, 2005 (2 of 4) - page 23
- Table 7: Phase I cancer vaccines in development, 2005 (3 of 4) - page 24
- Table 8: Phase I cancer vaccines in development, 2005 (4 of 4) - page 25
- Table 9: Therapeutic pipeline cancer vaccines by developmental phase & class, 2005 - page 26
- Table 10: Pipeline cancer vaccines by indication, 2005 - page 29
- Table 11: Proportion of personalized versus generalized cancer vaccines, 2005 - page 32
- Table 12: Companies/research institutions with three or more pipeline cancer vaccines - page 35
- Table 13: Companies with most influential cancer vaccine pipelines - page 36
- Table 14: Forecast incidence and mortality of the major indications for cancer vaccines in the seven major pharmaceutical markets, 2005 - page 39
- Table 15: Late-phase pipeline cancer vaccine sales forecasts ($m), 2005-14 - page 39
- Table 16: Datamonitor drug assessment summary - page 42
- Table 17: Common mutations involved in tumor development - page 49
- Table 18: Forecast incidence of cancer across the seven major markets, 2005-13 - page 55
- Table 19: Three main categories of cancer vaccines exist - page 69
- Table 20: Advantages and disadvantages of cancer vaccines - page 75
- Table 21: Relative efficacy merits of cancer vaccines - page 75
- Table 22: Relative formulation merits of cancer vaccines - page 76
- Table 23: Currently marketed cancer vaccines, 2005 - page 77
- Table 24: Pipeline polyvalent cancer vaccines in Phase II and III clinical trials, 2005 - page 92
- Table 25: Pipeline polyvalent cancer vaccines in Phase I clinical trials, 2005 - page 93
- Table 26: Polyvalent cancer vaccines sales forecasts assumptions - page 102
- Table 27: Polyvalent cancer vaccines sales forecasts ($m), 2005-14 - page 102
- Table 28: Research, clinical and commercial attractiveness summary for pipeline polyvalent cancer vaccines - page 104
- Table 29: Pipeline antigen-based cancer vaccines in Phase III clinical trials, 2005 - page 106
- Table 30: Pipeline antigen-based cancer vaccines in Phase II clinical trials, 2005 - page 107
- Table 31: Pipeline antigen-based cancer vaccines in Phase I clinical trials, 2005 (1 of 2) - page 108
- Table 32: Pipeline antigen-based cancer vaccines in Phase I clinical trials, 2005 (2 of 2) - page 109
- Table 33: Antigen-specific cancer vaccines sales forecasts assumptions (1 of 3) - page 126
- Table 34: Antigen-specific cancer vaccines sales forecasts assumptions (2 of 3) - page 127
- Table 35: Antigen-specific cancer vaccines sales forecasts assumptions (3 of 3) - page 127
- Table 36: Antigen-specific cancer vaccines sales forecasts ($m), 2005-14 - page 128
- Table 37: Research, clinical and commercial attractiveness summary for pipeline antigen-specific cancer vaccines (1 of 3) - page 130
- Table 38: Research, clinical and commercial attractiveness summary for pipeline antigen-specific cancer vaccines (2 of 3) - page 131
- Table 39: Research, clinical and commercial attractiveness summary for pipeline antigen-specific cancer vaccines (3 of 3) - page 131
- Table 40: Pipeline dendritic cell cancer vaccines in clinical trials, 2005 - page 134
- Table 41: Dendritic cell cancer vaccines sales forecasts assumptions - page 137
- Table 42: Dendritic cell cancer vaccines sales forecasts ($m), 2005-14 - page 138
- Table 43: Research, clinical and commercial attractiveness summary for pipeline dendritic cell cancer vaccines - page 139
- Table 44: Datamonitor drug assessment parameters - page 148
- List of Figures
- Figure 1: Antigen-specific vaccines dominate the pipeline - page 26
- Figure 2: Antigen-specific vaccines dominate all phases of development - page 27
- Figure 3: 'Big four' tumor types, plus melanoma & RCC remain popular indications - page 29
- Figure 4: Generalized vaccines dominate the cancer vaccine pipeline - page 33
- Figure 5: Small biotechnology companies dominate cancer vaccines R&D pipeline - page 34
- Figure 6: Pipeline polyvalent cancer vaccines sales forecasts, 2005-14 - page 40
- Figure 7: Pipeline antigen-specific cancer vaccines sales forecasts, 2005-14 - page 41
- Figure 8: Pipeline dendritic cell cancer vaccines sales forecasts, 2005-14 - page 41
- Figure 9: Datamonitor drug assessment summary for pipeline polyvalent cancer vaccines - page 42
- Figure 10: Datamonitor drug assessment summary for pipeline antigen-specific cancer vaccines - page 43
- Figure 11: Datamonitor drug assessment summary for pipeline dendritic cell cancer vaccines - page 44
- Figure 12: Significant challenges stand in the way of successful cancer vaccine commercialization - page 45
- Figure 13: Global oncology sales, 2002-09 - page 53
- Figure 14: Oncology pipeline, 2003 - page 54
- Figure 15: Forecast incidence of cancer across the seven major markets, 2005-13 - page 55
- Figure 16: Increasing combined incidence for breast, lung, prostate and colorectal cancer with increasing age, 2003 - page 56
- Figure 17: Incidence increases, while the rate of cure and death reduces disease prevalence - page 57
- Figure 18: Point prevalence for colorectal and lung cancer differs markedly despite similar rates of incidence - page 58
- Figure 19: Unmet needs in cancer - page 61
- Figure 20: To achieve success, cancer vaccines need to overcome immune tolerance - page 68
- Figure 21: Disadvantages associated with cancer vaccines are currently more significant than advantages - page 90
- Figure 22: Sales of Canvaxin and Oncophage restricted by size of target melanoma patient population - page 103
- Figure 23: Canvaxin appears most commercially attractive, while GVAX appears most research and clinically attractive - page 104
- Figure 24: Sales forecasts appear low due to the relatively cheap manufacturing costs of antigen-specific vaccines - page 128
- Figure 25: Lack of compelling clinical evidence makes differentiation of antigen-specific products difficult - page 132
- Figure 26: Provenge is the clear leader of the dendritic cell class of vaccines - page 138
- Figure 27: Provenge is the obvious market leader with this class of cancer vaccines - page 139
- Figure 28: Example of Datamonitor drug assessment scorecard - page 149
- Figure 29: Example of Datamonitor drug assessment graph - page 150
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