Innovative Targeted Oncology 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
- Scope of analysis - page 3
- Datamonitor insight into the targeted therapies market - page 3
- CHAPTER 2 PIPELINE OVERVIEW - page 20
- Pipeline overview - page 20
- Pipeline by developmental phase & class of drug - page 21
- Signal transduction inhibitors and angiogenesis inhibitors constitute over half the current targeted therapies pipeline - page 21
- Signal transduction inhibitors & angiogenesis inhibitors dominate due to their wide applicability for use and proven success in the market to date - page 23
- Setbacks suffered by Genta's Genasense may have deterred other developers of apoptosis stimulators - page 23
- The specificity of monoclonal antibody target means patient potential is restricted, however, success of Rituxan may spur developers on - page 24
- The HDAC inhibitors & cell cycle regulators are restricted in terms of potential molecular target, hence their minimal presence in the pipeline - page 24
- The current late-phase pipeline is relatively sparse due to the novelty of this market - page 24
- As time progresses, the late-phase pipeline will flourish as early-phase candidates move forward in development - page 24
- Signal transduction inhibitors and angiogenesis inhibitors constitute over half the current targeted therapies pipeline - page 21
- Pipeline by molecular target - page 25
- Signal transduction inhibitors - page 25
- The EGFR and multiple tyrosine kinases remain the focus of development as targets for signal transduction inhibitors - page 25
- Angiogenesis inhibitors - page 28
- The VEGFR and multiple tyrosine kinases remain the focus of development as targets for angiogenesis inhibitors - page 28
- Apoptosis stimulators - page 30
- Due to a lack of information from developers, a popular target for apoptosis is difficult to identify - page 30
- HDAC inhibitors - page 31
- Cell cycle regulators - page 32
- Utility of CDK as a target comes from known mutation/overexpression in some malignancies - page 32
- Other monoclonal antibodies - page 33
- The CD family of proteins allows for a highly specific target, with proven success via Rituxan - page 33
- Signal transduction inhibitors - page 25
- Pipeline by indication - page 35
- The 'big four' tumor types, plus melanoma and RCC are the most popular indications for development - page 36
- Constituting over half of all newly diagnosed cancer cases, the 'big four' tumor types offer significant commercial potential - page 36
- Melanoma and RCC are well characterized in terms of tumor growth drivers, thus making them ideal indications for the development of targeted therapies - page 37
- Non-Hodgkin's lymphoma dominates the pipeline within the hematological malignancies - page 37
- Based on incidence rates, non-Hodgkin's lymphoma is the most commercially attractive hematological indication for development - page 38
- Pipeline compounds for leukemia are similar across the different types, due to potential for horizontal expansion - page 38
- The 'big four' tumor types, plus melanoma and RCC are the most popular indications for development - page 36
- Pipeline by company - page 38
- At least 138 companies are involved in the current targeted therapies pipeline - page 38
- The majority of pipeline compounds are in early-phase trials, hence two-thirds of companies involved are small biotechnology firms - page 38
- Top three companies in terms of marketed and pipeline products are Genentech, AstraZeneca and Pfizer - page 39
- Genentech - page 39
- AstraZeneca - page 42
- Pfizer - page 43
- At least 138 companies are involved in the current targeted therapies pipeline - page 38
- Key metrics - page 45
- Datamonitor pipeline assessment summary - page 49
- CHAPTER 3 PIPELINE DYNAMICS - page 54
- A diverse range of disease subtypes - page 54
- Genetic basis of cancer evolution - page 54
- Tumorigenesis is the result of cooperative accumulated mutations - page 56
- Existing pharmacotherapy approaches provide limited treatment benefit - page 56
- Cytotoxic drugs lack specificity - page 57
- Hormonal or endocrine therapy provides incremental benefit in selected tumors - page 57
- Optimizing current treatment strategies is paramount - page 57
- The emergence of targeted treatment heralds a revolution in cancer pharmacotherapy - page 57
- Dynamic cancer market offers significant commercial opportunity - page 58
- Ongoing sales growth drives the market - page 58
- Intensive R&D produces a rich developmental pipeline - page 59
- Growing patient population and significant unmet needs propel innovation in the cancer market - page 60
- Cancer epidemiology - an expanding patient base - page 60
- Significant areas of unmet need persist - page 64
- Clinical and strategic threats to the commercialization of cancer drugs - page 67
- Progressively rising R&D costs threaten industry productivity - page 67
- High attrition rates can be mitigated by improved strategic decision-making - page 68
- Lengthening drug approval process a consequence of increased regulatory demands - page 68
- Pharmacoeconomic pressures drive payers to implement restrictive pricing and reimbursement policies - page 68
- Increased therapeutic and generic competition results in reduced periods of market exclusivity - page 69
- Segmentation of market will require changes in clinical trial methodology - page 70
- Progressively rising R&D costs threaten industry productivity - page 67
- CHAPTER 4 MARKET DEFINITION & PIPELINE CLASSIFICATION - page 71
- Targeted therapies overview - page 71
- The development of innovative targeted therapies - page 71
- Current therapies adversely affect non-malignant cells - page 71
- Innovative targeted therapies can address novel properties of tumor cells to selectively target them over normal cells - page 71
- Key issue is the identification of targets unique to cancer cells - page 72
- The development of innovative targeted therapies - page 71
- Market definition - page 72
- L1X3 - Antineoplastic monoclonal antibodies - page 72
- L1X9 - All other antineoplastics - page 73
- Classification of pipeline products - page 74
- Signal transduction inhibitors - page 74
- A plethora of potential targets along the signaling cascade exist - page 74
- Several signal transduction inhibitors have reached the market, bringing with them their own sets of issues for consideration - page 75
- Angiogenesis inhibitors - page 76
- Angiogenesis as a normal biological process - page 76
- Angiogenesis is known to be abberant in tumor cell proliferation - page 76
- Angiogenesis inhibitors as viable antitumor agents can target a number of pathways - page 78
- At present, only one angiogenesis inhibitor exists in the market - page 79
- Apoptosis stimulators - page 79
- Cell death can be induced via a number of different pathways - page 79
- To date, only one apoptosis stimulator has reached the market - page 80
- Histone deacetylase inhibitors - page 80
- Despite relative immaturity of development in this class of drugs, the potential to enhance current therapies exists - page 80
- Cell cycle inhibitors - page 81
- Despite ongoing R&D efforts, all current candidates remain in the Phase II stage of development - page 81
- Signal transduction inhibitors - page 74
- Pipeline comparator - page 82
- Current market situation - page 83
- Targeted therapies overview - page 71
- CHAPTER 5 MARKETED PRODUCTS FORECAST ANALYSIS - page 86
- Country-specific assumptions and effects - page 86
- Effect of Medicare Modernization Act in the US - page 86
- Biennial price cuts in Japan - page 86
- National Institute of Clinical Excellence in the UK - page 86
- Product assumptions and effects - page 87
- Signal transduction inhibitors - page 87
- Erbitux (cetuximab) - page 87
- Gleevec (imatinib) - page 89
- Herceptin (trastuzumab) - page 92
- Iressa (gefitinib) - page 93
- Tarceva (erlotinib) - page 95
- Targretin (bexarotene) - page 98
- Angiogenesis inhibitors - page 99
- Avastin (bevacizumab) - page 99
- Apoptosis stimulators - page 102
- Velcade (bortezomib) - page 102
- Other monoclonal antibodies - page 104
- Bexxar (tositumomab) - page 104
- Campath (alemtuzumab) - page 105
- Mylotarg (gemtuzumab) - page 106
- MabThera/Rituxan (rituximab) - page 107
- Zevalin (ibritumomab) - page 109
- Others - page 110
- Ontak (denileukin) - page 110
- Signal transduction inhibitors - page 87
- Forecasts - page 111
- Country-specific assumptions and effects - page 86
- CHAPTER 6 PIPELINE SIGNAL TRANSDUCTION INHIBITORS ANALYSIS & FORECASTS - page 112
- Pipeline overview - page 112
- Onyx Pharmaceuticals/Bayer's sorafenib (BAY 43-9006) - page 117
- Drug profile - page 117
- Multi-targeted approach allows for clinical development in a wide range of tumors - page 117
- Clinical trial data - page 118
- Sorafenib in RCC moves into preregistration - page 118
- Potential for monotherapy and combination therapy in HCC - page 119
- Combination therapy provides opportunity in malignant melanoma - page 119
- Phase II clinical trials - page 120
- Acceptable toxicity profile - page 120
- Datamonitor comments - page 121
- Despite sorafenib's convincing single-agent activity, full potential will lie in combination regimens - page 121
- Potential first-to-market status and collaboration will ensure sorafenib is the leading multi-kinase inhibitor - page 121
- Drug profile - page 117
- Pfizer's Sutent (sunitinib malate) - page 122
- Drug profile - page 122
- Development is ongoing in a variety of tumors due to wide applicability of use of Sutent - page 122
- Clinical trial data - page 123
- Sutent shows significant activity among refractory GIST patients with no alternative treatment options - page 123
- Significant activity shown in second-line treatment of RCC, though ongoing Phase III study is exploring first-line Sutent monotherapy - page 124
- Ongoing Phase II trial in breast cancer following encouraging preliminary results - page 125
- Activity shown in difficult to treat population with neuroendocrine tumors, although large-scale trials are yet to be initiated - page 126
- Phase II clinical trials - page 126
- Majority of Sutent's toxicities are mild in nature - page 127
- Datamonitor comments - page 127
- Initial regulatory approval will come via GIST patients, although product expansion will need to occur to increase commercial potential - page 127
- Pfizer's presence will be advantageous once Sutent gains marketing approval - page 128
- Drug profile - page 122
- Abbott Laboratories' Xinlay (atrasentan) - page 128
- Drug profile - page 128
- Xinlay's target receptor plays a key role in cancer cell proliferation - page 128
- Clinical trial data - page 129
- ODAC decision indicates low probability of Xinlay being granted FDA approval for prostate cancer - page 129
- Activity of Xinlay in NSCLC similar to standard chemotherapy - page 130
- Other trials - page 131
- Datamonitor comments - page 131
- Clinical benefit among a patient population with few treatment options means Xinlay could fulfill a significant unmet need - page 131
- Abbott's favorable position in the prostate cancer market will be invaluable in Xinlay's market potential - page 132
- Drug profile - page 128
- Abgenix/Amgen's ABX-EGF (panitumumab) - page 132
- Drug profile - page 132
- Overexpression of EGFR makes an ideal target for ABX-EGF development - page 132
- Clinical trial data - page 133
- ABX-EGF shows promise as monotherapy or combination therapy across a range of treatment settings for colorectal cancer - page 133
- Addition of ABX-EGF appears to enhance standard chemotherapy in NSCLC - page 135
- Poor results as a single agent in RCC - page 135
- Termination of development in prostate cancer - page 136
- Main side effect is a potential indicator of ABX-EGF activity - page 136
- Datamonitor comments - page 136
- Humanized nature of ABX-EGF holds some advantages over competitor EGFR inhibitors - page 136
- Way forward for Amgen lies in ABX-EGF combination regimens and potential development of biomarker - page 137
- Amgen's presence will ensure success, although profitability may increase by targeting earlier lines of therapy - page 138
- Drug profile - page 132
- GlaxoSmithKline's lapatinib (GW-572016) - page 139
- Drug profile - page 139
- Lapatinib is unique among the EGFR inhibitors by targeting two receptor tyrosine kinases - page 139
- Clinical trial data - page 140
- HER-2 overexpression in breast cancer justifies validity of lapatinib's target - page 140
- Limited single-agent activity indicates combination regimens including lapatinib are the way forward in NSCLC - page 142
- Limited activity has terminated development of lapatinib in colorectal cancer - page 143
- Modest activity in urothelial tumors, although unclear whether GlaxoSmithKline intends to pursue this indication - page 143
- Infrequent incidence of Grade 3 or higher toxicity - page 144
- Datamonitor comments - page 144
- Initial approval in niche breast cancer indication will expedite subsequent approvals, with potential blockbuster status for lapatinib - page 144
- GlaxoSmithKline needs to account for deficiency in oncology market experience to take full advantage of lapatinib's potential - page 145
- Drug profile - page 139
- Schering-Plough's Sarasar (lonafarnib) - page 146
- Drug profile - page 146
- Previously wide range of developmental indications for Sarasar has been reduced to just two - page 146
- Clinical trial data - page 146
- Main focus of Sarasar development in MDS, where greatest antitumor activity is shown - page 146
- Lack of efficacy has led to termination of pivotal Phase III trial in NSCLC - page 147
- Lack of clinical data makes it difficult to judge Sarasar's potential in breast cancer - page 148
- Benefit shown in advanced head and neck cancer, although no further trials have been announced - page 148
- Limited activity as a single agent, although Sarasar may show potential in combination therapy in pancreatic cancer - page 148
- Despite encouraging Phase II results in urothelial tract carcinoma, no further clinical trials are planned - page 149
- Lack of single-agent activity in colorectal cancer has halted development in this indication - page 150
- Mild toxicity in the majority of patients, although Grade 3 events do occur - page 150
- Datamonitor comments - page 150
- The FDA's recent rejection of Johnson & Johnson's Zarnestra may reduce the time between launches of the two farnesyl transferase inhibitors - page 150
- Presence in oncology market will aid commercialization of Sarasar - page 151
- Drug profile - page 146
- Wyeth's temsirolimus (CCI-779) - page 152
- Drug profile - page 152
- Temsirolimus inhibits a key pathway in tumor cell proliferation - page 152
- Clinical trial data - page 152
- Encouraging response rates seen for temsirolimus in combination with standard interferon-alfa for RCC in Phase I trials are being further investigated - page 152
- Substantial antitumor activity in Phase II trials in mantle cell lymphoma led to initiation of a Phase III trial in January 2005 - page 153
- Temsirolimus shows activity as a single agent and in combination with hormonal therapy in breast cancer - page 154
- Temsirolimus shows some activity in SCLC, although Wyeth has not stated its intention to pursue this indication - page 155
- Temsirolimus does not show activity as a single agent in melanoma - page 155
- Despite encouraging results, Wyeth is not pursuing glioblastome multiforme as a potential indication for temsirolimus - page 155
- Mild toxicity means temsirolimus is well tolerated - page 156
- Datamonitor comments - page 156
- Lucrative opportunites exist for temsirolimus, although broad commercialization would be expedited via an approval in a niche indication - page 156
- Prior commercialization of Mylotarg has given Wyeth the experience to launch temsirolimus successfully - page 157
- Drug profile - page 152
- AstraZeneca's Zactima (ZD-6474) - page 158
- Drug profile - page 158
- Zactima's ability to inhibit both angiogenesis and signal transduction should in theory result in greater efficacy in certain patient subsets - page 158
- Clinical trial data - page 158
- Phase III trials investigating Zactima in NSCLC are planned for second half of 2005 - page 158
- Phase II trial in multiple myeloma failed to meet primary endpoint - page 159
- Other trials - page 160
- Datamonitor comments - page 160
- Zactima's survival benefit in NSCLC needs to be convincing in order to compete with Tarceva - page 160
- AstraZeneca's strength in the oncology market will be key in Zactima's success - page 161
- Drug profile - page 158
- Janssen/Johnson & Johnson's Zarnestra (tipifarnib) - page 162
- Drug profile - page 162
- Previously wide range of developmental indications for Zarnestra have been reduced to just one - page 162
- Clinical trial data - page 163
- Following rejection of an NDA, the FDA requires Phase III data for Zarnestra in AML before regulatory approval can be considered - page 163
- Zarnestra shows activity in MDS, although further study is not planned in short-term future - page 164
- Negative Phase III trial results caused termination of development in pancreatic cancer - page 164
- Negative Phase III trial results caused termination of development in colorectal cancer - page 165
- Zarnestra development in breast cancer remains in Phase II trials - page 166
- Minimal activity in prostate cancer has terminated development in this indication - page 166
- Lack of activity in SCLC caused termination of Phase II trial - page 167
- Phase I trial is ongoing for Zarnestra in combination with chemotherapy in advanced NSCLC - page 167
- Despite modest activity in brain cancer, follow-up trials have not been initiated - page 167
- Mild toxicity is particularly significant since Zarnestra's main indication is for elderly AML patients where quality of life is a major issue - page 168
- Datamonitor comments - page 168
- FDA rejection has caused Zarnestra to lose its lead - page 168
- Focus on gene expression profiling may lead to fragmentation of the market - page 169
- Johnson & Johnson's experience will be invaluable to Zarnestra - page 169
- Zarnestra's niche indication may dilute effects of its probable first-to-market status loss - page 170
- Drug profile - page 162
- Bristol-Myers Squibb's dasatinib (BMS-354825) - page 170
- Drug profile - page 170
- Dasatinib shows potential to overcome Gleevec resistance - page 170
- Clinical trial data - page 171
- Dasatinib overcomes Gleevec resistance in CML patients - page 171
- Phase I study of dasatinib in solid tumors is ongoing - page 172
- Datamonitor comments - page 172
- Despite convincing clinical benefit, dasatinib already faces potential competition from Novartis's AMN-107 - page 172
- Bristol-Myers Squibb's extensive oncology experience will aid commercializatioan of dasatinib - page 173
- Drug profile - page 170
- Novartis's AMN-107 - page 173
- Drug profile - page 173
- AMN-107 shows potential for greater efficacy than Gleevec - page 173
- Clinical trial data - page 174
- AMN-107 confers significant activity in Gleevec-resistant CML - page 174
- Datamonitor comments - page 174
- AMN-107 in a race with Bristol-Myers Squibb's dasatinib to reach the market first - page 174
- An opportunity for Novartis to consolidate and expand its leading role in the CML therapy market - page 175
- Drug profile - page 173
- Kosan Biosciences' 17-AAG - page 175
- Drug profile - page 175
- Potential to disrupt a host of relevant oncology targets means 17-AAG shows a wide range of applicability - page 175
- Clinical trial data - page 177
- 17-AAG as a single agent induced disease stabilization in melanoma patients - page 177
- 17-AAG with docetaxel resulted in minor tumor responses - page 177
- 17-AAG with gemcitabine and cisplatin resulted in two partial responses - page 177
- Some evidence of 17-AAG activity in multiple myeloma - page 178
- Phase II trials - page 178
- Datamonitor comments - page 178
- Although 17-AAG's formulation may provide setbacks, commercial potential can be increased by developing biomarkers to judge response - page 178
- Kosan Biosciences should recruit the experience and resources of a key oncology player - page 179
- Drug profile - page 175
- Forecasts - page 180
- Datamonitor drug assessment summary - page 185
- CHAPTER 7 PIPELINE ANGIOGENESIS INHIBITORS ANALYSIS & FORECASTS - page 189
- Pipeline overview - page 189
- National Cancer Institute's CAI (L-651582, carboxyamidotriazole) - page 192
- Drug profile - page 192
- Clinical trials completed in a range of tumor types, although further development is unclear - page 192
- Clinical trial data - page 192
- Phase III trial failed to demonstrate any benefit of CAI over placebo in NSCLC - page 192
- Limited evidence for future development of CAI in RCC - page 193
- Some activity in ovarian cancer, although further development is unclear - page 193
- Datamonitor comments - page 193
- CAI left virtually redundant by Avastin and other late-stage pipeline angiogenesis inhibitors with superior clinical profiles - page 193
- Success of CAI depends solely on involvement of a pharmaceutical company, which is unlikely to occur - page 194
- Drug profile - page 192
- Æterna Zentaris's Neovastat (AE-941) - page 194
- Drug profile - page 194
- Development of Neovastat scaled down to focus solely on NSCLC - page 194
- Clinical trial data - page 195
- Final results from Phase III trial in NSCLC expected in 2006 - page 195
- Termination of Neovastat development in RCC following failure of Phase III to meet its primary endpoints - page 195
- Other indications - page 196
- Datamonitor comments - page 196
- If ongoing Phase III trial does not meet its primary endpoints, it could be the end for development of Neovastat - page 196
- Æterna Zentaris should secure a US marketing partner in order to increase commercial potential of Neovastat - page 196
- Drug profile - page 194
- Novartis/Schering AG's PTK-787 (vatalinib) - page 197
- Drug profile - page 197
- By targeting all known VEGFR tyrosine kinases, PTK-787 should show activity across a range of tumor types - page 197
- Clinical trial data - page 198
- Anticipated regulatory filing for PTK-787 in colorectal cancer delayed to 2007 following disappointing CONFIRM-1 interim results - page 198
- Recent initiation of the Phase II GOAL Study in NSCLC - page 199
- Phase II trial is ongoing for PTK-787 in glioblastoma multiforme - page 200
- Development in other tumors remains in early phases - page 200
- Majority of reported toxicities among 1,000 patients have been mild to moderate in nature - page 200
- Datamonitor comments - page 200
- PTK-787's distinct advantages could recoup any negative repurcussions from the CONFIRM-1 interim results - page 200
- Schering AG and particularly Novartis's prior oncology experience will be invaluable to PTK-787 - page 201
- Drug profile - page 197
- Pfizer's AG-13736 - page 202
- Drug profile - page 202
- Clinical trial data - page 202
- AG-13736 shows substantial antitumor activity in cytokine-refractory metastatic RCC - page 202
- AG-13736 does not confer significant activity as a single agent in AML and MDS - page 203
- Demonstration of AG-13736 activity in Phase I study in solid tumors forms the basis of ongoing Phase II trials - page 203
- Datamonitor comments - page 204
- With a strategic development plan, Pfizer may be able to overcome Avastin's leading position - page 204
- Pfizer's experience will be advantageous in the development of AG-13736 - page 204
- Forecasts - page 205
- Datamonitor drug assessment summary - page 207
- CHAPTER 8 PIPELINE APOPTOSIS STIMULATORS ANALYSIS & FORECASTS - page 210
- Pipeline overview - page 210
- Genta's Genasense (oblimersen) - page 213
- Drug profile - page 213
- Despite termination of Genta's agreement with Sanofi-Aventis, Genasense remains in development for a multitude of indications - page 213
- Clinical trial data - page 214
- Benefits of Genasense in CLL may not be enough to offset the addition of significant toxicity - page 214
- Long-term survival results of Genasense in malignant melanoma are of significance - page 215
- Disappointing Phase III trial results in multiple myeloma means status of further development is unclear - page 216
- Early-phase benefits of Genasense in AML require confirmation in Phase III clinical trial - page 217
- Lack of clinical data in NSCLC makes it difficult to judge Genasense's potential - page 218
- Encouraging Phase II results in prostate cancer, though Phase III trials have yet to be initiated - page 218
- Ongoing Phase II trial in SCLC will determine if patient benefit counters additional toxicity - page 219
- Promise shown in combination with rituximab in NHL, but randomized trials have yet to be initiated - page 219
- Genasense did not enhance activity of standard interferon-alfa in RCC - page 220
- Other trials - page 220
- Datamonitor comments - page 220
- Wide range of developmental indications for Genasense provides Genta with a significant commercial opportunity - page 220
- Termination of agreement with Sanofi-Aventis is a major setback for Genta - page 221
- Drug profile - page 213
- Telik's Telcyta (TLK286) - page 222
- Drug profile - page 222
- Synergy of Telcyta with standard cytotoxics may indicate a wide ranging applicability for use - page 222
- Clinical trial data - page 223
- Convincing Phase II results have initiated two large-scale Phase III trials in ovarian cancer - page 223
- Benefit of Telcyta in combination with standard chemotherapy shown in NSCLC - page 224
- Telcyta shows some activity as a single agent in breast cancer, although final Phase II results have yet to be published - page 226
- Uncertain status of Telcyta in colorectal cancer - page 226
- Datamonitor comments - page 227
- Telik should seek initial approval of Telcyta in ovarian cancer, which should expedite subsequent submissions - page 227
- In light of the competition Tarceva will provide for Telcyta, Telik would be prudent in seeking a commercialization partner - page 228
- Drug profile - page 222
- Xenova's TransMID (XR-311) - page 228
- Drug profile - page 228
- TransMID's target is highly relevant in brain cancer - page 228
- Clinical trial data - page 229
- Encouraging Phase II results, active clinical trial program and fast-track designation will drive development of TransMID - page 229
- Datamonitor comments - page 230
- Cumbersome infusion schedule and administration may detract from TransMID's broad clinical benefit - page 230
- Although Xenova has secured several marketing partnerships, a glaring omission is one in the lucrative US market - page 230
- Drug profile - page 228
- Forecasts - page 231
- Datamonitor drug assessment summary - page 233
- CHAPTER 9 PIPELINE HISTONE DEACETYLASE INHIBITORS ANALYSIS & FORECASTS - page 236
- Pipeline overview - page 236
- Gloucester Pharmaceuticals' FK-228 (depsipeptide) - page 237
- Drug profile - page 237
- Broad range of HDAC inhibition should theoretically provide increased efficacy - page 237
- Clinical trial data - page 238
- Encouraging results in cutaneous T-cell lymphoma require replication in ongoing Phase III clinical trial - page 238
- A lack of clinical data exists, despite FK-228's Phase II status in prostate cancer and RCC - page 238
- Datamonitor comments - page 239
- FK-228 likely to become the first HDAC inhibitor to reach the market - page 239
- Commercial success of FK-228 will rely on Gloucester Pharmaceuticals collaborating with large pharma - page 239
- Drug profile - page 237
- Forecasts - page 240
- Datamonitor drug assessment summary - page 241
- CHAPTER 10 OTHER PIPELINE MONOCLONAL ANTIBODIES ANALYSIS & FORECASTS - page 244
- Pipeline overview - page 244
- Millennium Pharmaceuticals/BZL Biologics's MLN-2704 - page 246
- Drug profile - page 246
- MLN-2704 has been developed specifically for prostate cancer - page 246
- Clinical trial data - page 247
- High doses of MLN-2704 resulted in tumor response and reduction in PSA levels in progressive, metastatic HRPC patients - page 247
- Datamonitor comments - page 248
- Significant opportunity lies in the prostate cancer market, although future expansion could occur within other tumor types - page 248
- Experience gained in commercialization of Velcade will be invaluable in the development of MLN-2704 - page 249
- Drug profile - page 246
- Forecasts - page 249
- Datamonitor drug assessment summary - page 251
- CHAPTER 11 COMMERCIAL IMPACT & LIFECYCLE MANAGEMENT: CASE STUDIES - page 253
- Introduction - page 253
- Case study 1 - page 253
- Iressa and Tarceva: why the difference? - page 253
- How have two nearly identical drugs realized such varying levels of success in the NSCLC market? - page 253
- Iressa's Phase II survival benefit was sufficient to garner FDA approval - page 254
- Concerns over Iressa's potential toxicity restricted its use in Japan - page 255
- FDA approval of Tarceva was based on a Phase III trial that demonstrated a two-month survival benefit in the third-line NSCLC setting - page 255
- Phase III ISEL trial comparing Iressa with placebo in advanced NSCLC failed to show survival benefit - page 256
- Negative repercussions of the Iressa's failed Phase III trial - page 257
- Tarceva's potential is currently limited by Alimta in the second-line setting, although line extensions will increase uptake and sales - page 257
- What if Iressa had not failed? - page 258
- Could Iressa pose a threat to Tarceva? - page 258
- Future opportunities are plentiful for Tarceva and Iressa - page 259
- Iressa and Tarceva: why the difference? - page 253
- Case study 2 - page 260
- Strategies for success: Genentech - page 260
- A leading oncology player with winning strategies - page 260
- Strengths and weaknesses of a collaborative partnership - page 261
- The prime example - page 262
- Strategies for success: Novartis - page 263
- An entirely new strategy for the pharmaceutical industry - page 263
- Early-phase development was slow... - page 263
- ...although subsequent approval and launch was remarkably quick - page 264
- Approval for a second indication granted only nine months after Gleevec's initial approval - page 265
- Opportunities for continued growth exist... - page 265
- ...although some drawbacks and threats have arisen - page 266
- The rewards of this strategy are very attractive to developers - page 266
- Strategies for success: Genentech - page 260
- Case study 3 - page 267
- The pharmacoeconomic challenges associated with targeted therapies - page 267
- Unique pharmacoeconomic challenges will arise as targeted therapies are included in standard chemotherapy regimens - page 267
- The cost of standard chemotherapy for cancer - page 267
- The inclusion of targeted therapies into standard treatment regimens - page 268
- The impact of monoclonal antibody targeted therapies - page 268
- The impact of small molecule targeted therapies - page 269
- The problem of adding targeted therapies to standard chemotherapy regimens - page 271
- Further effects of pharmacoeconomic issues - page 271
- Communicating the value of targeted therapies - page 272
- The pharmacoeconomic challenges associated with targeted therapies - page 267
- APPENDIX A - MARKET DATA & MAJOR BRAND KEY FACTS - page 274
- L1X3 (antineoplastic monoclonal antibodies) class market data - page 274
- L1X9 (all other neoplastics) class market data - page 278
- Sales data and forecasts - page 281
- PowerPoint Executive Presentation - page 281
- APPENDIX B - SALES FORECASTS - page 282
- US forecasts - page 282
- Japan forecasts - page 284
- France forecasts - page 285
- Germany forecasts - page 286
- Italy forecasts - page 287
- Spain forecasts - page 288
- UK forecasts - page 289
- EU5 forecasts - page 290
- Global forecasts - page 291
- APPENDIX C - page 293
- List of tables - page 293
- List of figures - page 299
- Methodology - page 302
- Datamonitor forecast methodology - page 302
- Forecasts for marketed drugs - page 302
- Forecasts for pipeline drugs - page 303
- Datamonitor drug assessment methodology - page 304
- Datamonitor forecast methodology - page 302
- List of abbreviations - page 307
- Contributing experts - page 309
- US opinion leader 1 - page 309
- US opinion leader 2 - page 319
- Bibliography - page 326
- About Datamonitor - page 346
- About Datamonitor Healthcare - page 346
- About the Oncology analysis team - page 347
- Disclaimer - page 348
- List of Tables
- Table 1: Targeted therapies in preregistration, 2005 - page 20
- Table 2: Targeted therapies in Phase III development, 2005 - page 21
- Table 3: Pipeline targeted therapies by development phase & class of drug, 2005 - page 22
- Table 4: Pipeline signal transduction inhibitors by target, 2005 - page 26
- Table 5: Pipeline angiogenesis inhibitors in development by target, 2005 - page 28
- Table 6: Pipeline apoptosis stimulators in development by target, 2005 - page 30
- Table 7: Pipeline cell cycle regulators in development by target, 2005 - page 32
- Table 8: Pipeline monoclonal antibodies in development by target, 2005 - page 33
- Table 9: Pipeline targeted therapies by indication, 2005 - page 35
- Table 10: Genentech's marketed oncology portfolio, 2005 - page 40
- Table 11: Genentech's pipeline oncology portfolio, 2005 - page 41
- Table 12: AstraZeneca's marketed oncology portfolio, 2005 - page 42
- Table 13: AstraZeneca's pipeline oncology portfolio, 2005 - page 43
- Table 14: Pfizer's marketed oncology portfolio, 2005 - page 43
- Table 15: Pfizer's pipeline oncology portfolio, 2005 - page 44
- Table 16: Late-phase pipeline targeted therapies sales forecasts ($m), 2005-14 - page 45
- Table 17: Datamonitor drug assessment summary - page 49
- Table 18: Common mutations involved in tumor development - page 55
- Table 19: Forecast incidence of cancer across the seven major markets, 2005-13 - page 60
- Table 20: Examples of naturally occurring angiogenesis stimulators - page 78
- Table 21: Current marketed products in the targeted therapies market, (1 of 2) - page 83
- Table 22: Current marketed products in the targeted therapies market, (2 of 2) - page 84
- Table 23: Targeted therapies sales in the seven major markets, 2003-04 - page 85
- Table 24: Late-phase pipeline signal transduction inhibitors in development, 2005 (1 of 2) - page 112
- Table 25: Late-phase pipeline signal transduction inhibitors in development, 2005 (2 of 2) - page 113
- Table 26: Phase II pipeline signal transduction inhibitors in development, 2005 (1 of 2) - page 114
- Table 27: Phase II pipeline signal transduction inhibitors in development, 2005 (2 of 2) - page 115
- Table 28: Phase I pipeline signal transduction inhibitors in development, 2005 - page 116
- Table 29: Ongoing clinical trials involving sorafenib - page 117
- Table 30: Ongoing clinical trials involving Sutent - page 123
- Table 31: Ongoing clinical trials involving Xinlay - page 129
- Table 32: Ongoing clinical trials involving ABX-EGF - page 133
- Table 33: Ongoing clinical trials involving lapatinib - page 140
- Table 34: Ongoing clinical trials involving Sarasar - page 146
- Table 35: Ongoing clinical trials involving temsirolimus - page 152
- Table 36: Ongoing clinical trials involving Zactima - page 158
- Table 37: Ongoing clinical trials involving Zarnestra - page 162
- Table 38: Ongoing clinical trials involving dasatinib - page 170
- Table 39: Ongoing clinical trials involving AMN-107 - page 173
- Table 40: Ongoing clinical trials involving 17-AAG - page 176
- Table 41: Xinlay & Sutent forecasting assumptions - page 180
- Table 42: Sorafenib & ABX-EGF forecasting assumptions - page 181
- Table 43: Lapatinib & Sarasar forecasting assumptions - page 181
- Table 44: Temsirolimus & Zactima forecasting assumptions - page 182
- Table 45: Zarnestra, dasatinib & AMN-107 forecasting assumptions - page 182
- Table 46: Signal transduction inhibitors sales forecasts ($m), 2005-14 - page 183
- Table 47: Research/clinical and commercial attractiveness of pipeline signal transduction inhibitors (1 of 3) - page 185
- Table 48: Research/clinical and commercial attractiveness of pipeline signal transduction inhibitors (2 of 3) - page 186
- Table 49: Research/clinical and commercial attractiveness of pipeline signal transduction inhibitors (3 of 3) - page 186
- Table 50: Late-phase pipeline angiogenesis inhibitors in development, 2005 - page 189
- Table 51: Phase II pipeline angiogenesis inhibitors in development, 2005 - page 190
- Table 52: Phase I pipeline angiogenesis inhibitors in development, 2005 - page 191
- Table 53: Ongoing clinical trials involving Neovastat - page 194
- Table 54: Ongoing clinical trials involving PTK-787 - page 198
- Table 55: Ongoing clinical trials involving AG-13736 - page 202
- Table 56: PTK-787, Neovastat & AG-13736 forecasting assumptions - page 205
- Table 57: Angiogenesis inhibitors sales forecasts ($m), 2005-14 - page 205
- Table 58: Research/clinical and commercial attractiveness of pipeline angiogenesis inhibitors - page 207
- Table 59: Late-phase pipeline apoptosis stimulators in development, 2005 - page 210
- Table 60: Phase II pipeline apoptosis stimulators in development, 2005 (1 of 2) - page 211
- Table 61: Phase II pipeline apoptosis stimulators in development, 2005 (2 of 2) - page 212
- Table 62: Phase I pipeline apoptosis stimulators in development, 2005 - page 212
- Table 63: Ongoing clinical trials involving Genasense - page 213
- Table 64: Ongoing clinical trials involving Telcyta - page 223
- Table 65: Ongoing clinical trials involving TransMID - page 229
- Table 66: Genasense forecasting assumptions - page 231
- Table 67: Telcyta & TransMID forecasting assumptions - page 231
- Table 68: Apoptosis stimulators sales forecasts ($m), 2005-14 - page 232
- Table 69: Research/clinical and commercial attractiveness of pipeline apoptosis stimulators - page 233
- Table 70: Pipeline histone deacetylase inhibitors in development, 2005 - page 236
- Table 71: Ongoing clinical trials involving FK-228 - page 237
- Table 72: FK-228 forecasting assumptions - page 240
- Table 73: FK-228 sales forecasts ($m), 2005-14 - page 240
- Table 74: Research/clinical and commercial attractiveness of FK-228 - page 242
- Table 75: Phase II/III pipeline monoclonal antibodies in development, 2005 (1 of 2) - page 244
- Table 76: Phase II/III pipeline monoclonal antibodies in development, 2005 (2 of 2) - page 245
- Table 77: Phase I pipeline monoclonal antibodies in development, 2005 - page 246
- Table 78: Ongoing clinical trials involving MLN-2704 - page 247
- Table 79: MLN-2704 forecasting assumptions - page 249
- Table 80: MLN-2704 sales forecasts ($m), 2005-14 - page 250
- Table 81: Research/clinical and commercial attractiveness of MLN-2704 - page 251
- Table 82: Key Iressa & Tarceva events in the NSCLC market - page 254
- Table 83: Rituxan: key facts - page 274
- Table 84: Herceptin: key facts - page 275
- Table 85: Campath: key facts - page 275
- Table 86: Mylotarg: key facts - page 276
- Table 87: Bexxar: key facts - page 276
- Table 88: Avastin: key facts - page 277
- Table 89: Erbitux: key facts - page 277
- Table 90: Zevalin: key facts - page 278
- Table 91: Gleevec: key facts - page 278
- Table 92: Targretin: key facts - page 279
- Table 93: Iressa: key facts - page 279
- Table 94: Velcade: key facts - page 280
- Table 95: Tarceva: key facts - page 280
- Table 96: Ontak: key facts - page 281
- Table 97: Forecasts for antineoplastic monoclonal antibodies in the US, 2004-14 - page 282
- Table 98: Forecasts for all other antineoplastics in the US, 2004-14 - page 283
- Table 99: Forecasts for marketed targeted therapies in Japan, 2004-14 - page 284
- Table 100: Forecasts for marketed targeted therapies in France, 2004-14 - page 285
- Table 101: Forecasts for marketed targeted therapies in Germany, 2004-14 - page 286
- Table 102: Forecasts for marketed targeted therapies in Italy, 2004-14 - page 287
- Table 103: Forecasts for marketed targeted therapies in Spain, 2004-14 - page 288
- Table 104: Forecasts for marketed targeted therapies in the UK, 2004-14 - page 289
- Table 105: Forecasts for marketed targeted therapies in the EU5, 2004-14 - page 290
- Table 106: Global forecasts for antineoplastic monoclonal antibodies, 2004-14 - page 291
- Table 107: Global forecasts for all other antineoplastics, 2004-14 - page 292
- Table 108: Datamonitor drug assessment parameters - page 304
- Table 109: Abbreviations used in Pipeline/Commercial Insight: Innovative Targeted Therapies (1 of 2) - page 307
- Table 110: Abbreviations used in Pipeline/Commercial Insight: Innovative Targeted Therapies (2 of 2) - page 308
- List of Figures
- Figure 1: Signal transduction inhibitors and angiogenesis inhibitors form the bulk of the 2005 targeted therapies pipeline - page 22
- Figure 2: A plethora of current early-phase agents will come to light in the short-term future - page 25
- Figure 3: Targeting multiple tyrosine kinases appears to be the current trend in R&D - page 26
- Figure 4: Targeting the primary VEGF receptor appears the most popular development strategy - page 29
- Figure 5: The majority of developmental agents affect unspecified apoptosis targets - page 31
- Figure 6: CDK appears to be the primary developmental target for the cell cycle regulators - page 32
- Figure 7: The CD family of proteins appears most favorable for development - page 34
- Figure 8: Big four tumor types, plus melanoma and RCC, remain popular indications - page 36
- Figure 9: Hematological indications with the highest incidence dominate the developmental pipeline - page 37
- Figure 10: The majority of pipeline compounds are in early-phase trials, therefore a high level of fragmentation exists - page 39
- Figure 11: Pipeline signal transduction inhibitors sales forecasts, 2005-14 - page 46
- Figure 12: Pipeline angiogenesis inhibitors sales forecasts, 2005-14 - page 46
- Figure 13: Pipeline apoptosis stimulators sales forecasts, 2005-14 - page 47
- Figure 14: Pipeline HDAC inhibitors sales forecasts, 2005-14 - page 47
- Figure 15: Pipeline monoclonal antibodies sales forecasts, 2005-14 - page 48
- Figure 16: Datamonitor drug assessment summary for pipeline signal transduction inhibitors - page 50
- Figure 17: Datamonitor drug assessment summary for pipeline angiogenesis inhibitors - page 51
- Figure 18: Datamonitor drug assessment summary for pipeline apoptosis stimulators - page 52
- Figure 19: Datamonitor drug assessment summary for pipeline HDAC inhibitors - page 53
- Figure 20: Datamonitor drug assessment summary for pipeline monoclonal antibodies - page 53
- Figure 21: Global oncology sales, 2002-09 - page 58
- Figure 22: Oncology pipeline, 2003 - page 59
- Figure 23: Forecast incidence of cancer across the seven major markets, 2005-13 - page 61
- Figure 24: Increasing combined incidence for breast, lung, prostate and colorectal cancer with increasing age, 2003 - page 61
- Figure 25: Incidence increases, while the rate of cure and death reduces disease prevalence - page 62
- Figure 26: Point prevalence for colorectal and lung cancer differs markedly despite similar rates of incidence - page 63
- Figure 27: Unmet needs in cancer - page 67
- Figure 28: The process of tumor angiogenesis - page 77
- Figure 29: The multiple tyrosine kinase inhibitors will achieve the greatest commercial success - page 183
- Figure 30: The multiple tyrosine kinase inhibitors appear most attractive in terms of research/clinical and commercial aspects - page 187
- Figure 31: PTK-787 is currently the front runner of the angiogenesis inhibitors due to the high patient potential of its indication - page 206
- Figure 32: Candidates with the backing of key oncology players appear most attractive among the pipeline angiogenesis inhibitors - page 208
- Figure 33: Genasense is the clear leader due to its wide range of developmental indications - page 232
- Figure 34: Route of administration may work against the pipeline apoptosis stimulators - page 234
- Figure 35: FK-228's sales are currently limited by its target indication - page 241
- Figure 36: A lack of clinical data and commercial experience currently limit FK-228's attractiveness - page 243
- Figure 37: MLN-2704's commercial potential will increase once indications outside of prostate cancer are explored - page 250
- Figure 38: Attractiveness of MLN-2704 will increase once development outside of prostate cancer is initiated - page 252
- Figure 39: Example of Datamonitor drug assessment scorecard - page 305
- Figure 40: Example of Datamonitor drug assessment graph - page 306
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