Pipeline Insight: Cancer Overview Emerging Therapeutic and Commercial Opportunities
Scope
Report Highlights
Reasons to Purchase
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE - page 2
- About the Oncology pharmaceutical analysis team - page 2
- CHAPTER 1 EXECUTIVE SUMMARY - page 3
- Scope of the analysis - page 3
- Datamonitor insight - page 4
- Brain cancer - page 4
- Breast Cancer - page 4
- Colorectal cancer - page 5
- Gastric cancer - page 5
- Head and neck cancer - page 6
- Hepatocellular carcinoma - page 6
- Non-small cell lung cancer - page 7
- Ovarian cancer - page 7
- Pancreatic cancer - page 8
- Prostate cancer - page 9
- Renal cell carcinoma - page 9
- Key metrics - page 10
- Incidence - page 10
- Sales forecasts - page 13
- CHAPTER 2 PIPELINE OVERVIEW - page 49
- High R&D interest in breast and non-small cell lung cancer - page 49
- Targeted therapies dominate but cytotoxics remain significant - page 51
- CHAPTER 3 PIPELINE DYNAMICS - page 63
- A diverse range of disease subtypes - page 63
- Genetic basis of cancer evolution - page 63
- TUMOROGENESIS IS THE RESULT OF CO-OPERATIVE ACCUMULATED MUTATIONS - page 65
- Existing pharmacotherapy approaches provide limited treatment benefit - page 65
- Cytotoxic drugs lack specificity - page 66
- Hormonal or endocrine therapy provides incremental benefit in selected tumors - page 66
- Optimizing current treatment strategies is paramount - page 66
- The emergence of targeted treatment heralds a revolution in cancer pharmacotherapy - page 66
- Dynamic cancer market offers significant commercial opportunity - page 67
- Ongoing sales growth drives the market - page 67
- Intensive R&D produces a rich developmental pipeline - page 68
- Growing patient population and significant unmet needs propel innovation in the cancer market - page 69
- Cancer epidemiology - an expanding patient base - page 69
- Significant areas of unmet need persist - page 71
- Clinical and strategic threats to the commercialization of cancer drugs - page 74
- Progressively rising R&D costs threaten industry productivity - page 74
- High attrition rates can be mitigated by improved strategic decision-making - page 75
- Lengthening drug approval process a consequence of increased regulatory demands - page 75
- Pharmacoeconomic pressures drive payers to implement restrictive pricing and reimbursement policies - page 76
- Increased therapeutic and generic competition leads to reduced periods of market exclusivity - page 76
- Segmentation of market will require changes in clinical trial methodology - page 77
- Progressively rising R&D costs threaten industry productivity - page 74
- CHAPTER 4 BREAST CANCER - page 78
- Overview - page 78
- Definition of breast cancer - page 79
- Four types of breast cancer exist - page 80
- Ductal carcinoma in situ (DCIS): the most common form of non-invasive breast cancer - page 80
- Lobular carcinoma in situ (LCIS) rarely develops into invasive disease - page 80
- Paget's disease is predominately associated with invasive disease - page 80
- Male breast cancer accounts for 1% of all breast carcinomas - page 80
- Genetics of breast cancer - page 80
- Diagnosis of breast cancer - page 81
- There are a number of prognostic factors of breast cancer - page 82
- Hormone receptor status - page 82
- Lymph node involvement - page 82
- Histologic grade - page 82
- HER-2/neu status - page 82
- S-phase status - page 83
- Four types of breast cancer exist - page 80
- Epidemiology of breast cancer - page 83
- Breast cancer remains the commonest cancer among women worldwide - page 83
- Current treatment options - page 86
- Standard treatment options are based primarily upon disease stage - page 86
- Stage I: breast-conserving surgery forms the mainstay of treatment - page 86
- Stage II: the use of systemic therapy is dependent upon a number of factors - page 86
- Stage III: due to the involvement of lymph nodes, adjuvant systemic therapy is crucial - page 87
- Stage IV: as treatment is largely palliative, antihormonal therapies are preferred to the cytotoxics - page 87
- Standard treatment options are based primarily upon disease stage - page 86
- Overview of current drug therapy options - page 88
- Adjuvant treatment options are varied - page 88
- Chemotherapy is recommended regardless of hormone-receptor status - page 88
- Tamoxifen remains the standard hormone treatment of adjuvant breast cancer - page 88
- Treatment of advanced disease - page 90
- Adjuvant treatment options are varied - page 88
- Unmet needs in breast cancer are significant - page 94
- Effective treatment for metastatic disease still remains elusive - page 95
- A wider range of treatment options is required for hormone receptor-negative patients - page 96
- Elderly patients remain an under-served population - page 97
- Stage III patients represent a missed opportunity - page 97
- A more convenient treatment is needed - page 98
- Earlier diagnosis via mammography is improving prognosis but screening awareness must remain - page 98
- Pipeline analysis - page 99
- Genentech/Roche's Avastin (bevacizumab) - page 103
- Avastin: the first anti-angiogenic agent to gain approval in cancer - page 103
- Clinical trial data - page 105
- Phase III trials show the addition of Avastin to paclitaxel doubles progression free survival in the first-line setting of locally recurrent/metastatic disease - page 105
- Avastin plus capecitabine Phase III study fails to improve survival in relapsed metastatic breast cancer patients - page 107
- Avastin's patient potential is significant because of its first-line locally advanced/metastatic target - page 108
- Introgen Therapeutics' Advexin (AD5CMV-p53/ INGN-201) - page 110
- Advexin is designed on the basis that over half of all tumors contain a mutated p53 tumor suppressor gene - page 110
- Clinical trial data - page 111
- Phase I monotherapy trial demonstrates Advexin's favorable safety profile - page 111
- Phase II neoadjuvant Advexin in combination with docetaxel and doxorubicin study leads to over 50% reduction in tumor size in all patients - page 112
- Advexin must demonstrate improved patient survival to impact the neoadjuvant breast cancer market - page 112
- Without Aventis' backing, Introgen will struggle to commercialize Advexin - page 113
- Eli Lilly's arzoxifene (LY-353381) - page 113
- Clinical trial data - page 114
- Phase IB breast cancer prevention trial demonstrates a 6% decrease in estrogen receptor expression - page 114
- Phase II breast cancer preventative study - page 114
- Phase II arzoxifene fails to statistically improve trial endpoints in locally advanced/metastatic breast tumor patients - page 115
- Arzoxifene's targeting of osteoporotic women at high risk of breast cancer offers a significant commercial opportunity] - page 116
- Lilly must use its marketing strengths to maximize arzoxifene's uptake - page 116
- YM Biosciences' tesmilifene - page 117
- Tesmilifene Phase III breast cancer development continues with interim analysis expected soon - page 117
- Clinical trial data - page 118
- Early-stage trials warrant a combination of tesmilifene plus doxorubicin - page 118
- First Phase III tesmilifene plus doxorubicin trial halted after failure to reach study endpoint, despite improving overall survival by 50%, and toxicity concerns - page 119
- Tesmilifene's patient potential is difficult to judge - page 121
- YM Biosciences may struggle to raise tesmilifene's profile - page 122
- Sonus Pharmaceuticals' Tocosol paclitaxel - page 123
- Tocosol paclitaxel is a cremophor-free Vitamin-E based formulation - page 123
- Clinical trial data - page 124
- Phase I Tocosol paclitaxel trial shows potential as a novel breast cancer agent - page 125
- Phase IIB trial demonstrates over seven-month progression-free survival without Grade 4 non-hematological adverse effects - page 125
- Tocosol paclitaxel potential patient population may be reduced in cost-constrained markets - page 129
- Schering AG's licensing deal will prove vital to raise Tocosol paclitaxel's profile - page 129
- GlaxoSmithKline's Tykerb/Tycerb (lapatinib) - page 130
- Tykerb/Tycerb is expected to file with the FDA and EMEA during H2 2006 following positive Phase III data - page 130
- Clinical trial data - page 132
- Tykerb shows promise for the treatment of refractory inflammatory HER-2 positive breast tumors with a 62% response rate - page 133
- Disappointing HER-2 positive brain metastases trial suggests Tykerb may not penetrate the blood-brain barrier as well as previously believed - page 133
- Phase II first-line HER-2 positive, locally advanced (IIIB/IIIC) or metastatic Tykerb trial demonstrates over 45% stable disease - page 134
- Phase II trial finds Tykerb leads to four-month progression-free survival in over 20% of Herceptin-refractory metastatic breast tumors - page 134
- Advanced solid HER-1/HER-2 positive tumors trial supports the use of Tykerb - page 135
- Phase III study announced at ASCO 2006 demonstrates Tykerb plus capecitabine leads to 49% reduction in the risk of tumor progression, but is associated with cardiac toxicities - page 136
- Tykerb's dual ERB targeting mechanism will lead to a significant patient potential - page 137
- GlaxoSmithKline's limited oncology portfolio will be bolstered by the arrival of Tykerb - page 139
- Sanofi-Aventis's XRP-9881 - page 140
- XRP-9881 has been in Phase III development for breast cancer since 2004 - page 140
- Clinical trial data - page 141
- Phase II trial demonstrates XRP-9881 has a greater survival benefit in taxane non-resistant breast tumors than taxane-resistant breast tumors - page 141
- XRP-9881's toxicity profile may limit its patient population - page 143
- Sanofi-Aventis must increase awareness of XRP-9881 - page 144
- Pipeline drug sales forecasts to 2016 - page 145
- Datamonitor drug assessment summary - page 147
- Genentech/Roche's Avastin (bevacizumab) - page 103
- CHAPTER 5 BRAIN CANCER - page 150
- Overview - page 150
- Definition of brain cancer - page 150
- Epidemiology of brain cancer - page 151
- Gliomas account for 77% of all malignant brain tumors - page 151
- The most virulent form of glioma, glioblastoma multiforme is the most frequently reported - page 153
- Current treatment options - page 155
- Surgery is the initial therapeutic approach - page 156
- Radiation therapy is employed to kill residual malignant cells - page 156
- Gliadel wafers can be inserted into resection cavity - page 156
- Long-term follow-up data demonstrate survival benefit of Gliadel wafer - page 156
- Before temozolomide systemic chemotherapy was of limited benefit - page 157
- Temozolomide is improving outlook for glioblastoma multiforme patients - page 157
- Some molecular markers have demonstrated prognostic utility regarding response to chemotherapy - page 158
- Loss of heterozygosity indicates response to lomustine, procarbazine and vincristine therapy in oligodendroglioma - page 158
- Hypermethylation of O6-methylguanine-DNA methyltransferase promoter indicates increased sensitivity to temozolomide in glioblastoma patients - page 158
- Unmet needs in glioma - page 160
- Pipeline analysis - page 160
- Enzastaurin, Eli Lilly's first targeted oncology drug - page 162
- Phase III trials initiated in March 2006 - page 163
- Enzastaurin demonstrates clinical benefit in recurrent or progressive glioma - page 163
- Enzastaurin will benefit from its favorable safety profile - page 164
- Ongoing trials will examine potential association of anticoagulation therapy, enzastaurin and intratumoral bleeds - page 164
- Enzastaurin demonstrates exciting activity in hard-to-treat cohort - page 165
- Enzastaurin fulfills significant unmet needs in recurrent setting - page 165
- Historical data of temozolomide sales suggest off-label use prior to approval - page 166
- Gleevec (imatinib) targets PDGF in glioblastoma multiforme - page 167
- Gleevec demonstrates activity in refractory glioblastoma multiforme - page 168
- Ongoing trials are examining Gleevec and hydroxyurea in glioblastoma multiforme - page 168
- Gleevec holds promise for GBM - page 168
- Cintredekin besudotox (IL13-PE38QQR; NK-408), Neopharm - page 169
- Neopharm anticipates filing in mid-2006 - page 169
- Updated Phase I/II trial data demonstrate significant survival advantage - page 170
- Phase I/II trial data formed the basis for Phase III trial design - page 170
- Peritumoral drug delivery offers increased overall survival - page 170
- IL13-PE38QQR impressive survival results required if uptake is to be secured - page 171
- Celtic Pharma acquires Xenova and TransMID (XR-311) - page 172
- Active clinical trial program and fast-track designation will drive development - page 172
- Cumbersome infusion schedule and administration may detract from TransMID's broad clinical benefit - page 173
- Cotara (131I-ch, TNT-1B, 131I-TNT), Peregrine Pharmaceuticals - page 173
- Peregrine has entered collaboration with New Approaches to Brain Tumor Therapy (NABTT) for a pivotal registration trial - page 174
- Phase II trials of Cotara demonstrated 100% increase in time-to-progression compared to the historical value of eight weeks - page 174
- Phase III trial designed to minimize inconvenience and reduce costs. - page 175
- Low physician awareness and lack of oncology experience may hinder Cotara's uptake - page 175
- Nimotuzumab (TheraCIM h-R3: as Theraloc in Europe), YM Biosciences/Center of Molecular Immunology/Oncoscience - page 176
- Phase III for pediatric pontine (brain stem) glioma - page 176
- Phase II pediatric trial demonstrated activity - page 176
- Positive efficacy and favorable toxicity data for Phase II trial results of nimotuzumab - page 177
- Phase III trial results required to verify the efficacy of this agent - page 177
- Pipeline drug sales forecasts to 2016 - page 178
- Datamonitor drug assessment summary - page 180
- Enzastaurin, Eli Lilly's first targeted oncology drug - page 162
- CHAPTER 6 COLORECTAL CANCER - page 182
- Overview - page 182
- Definition of colorectal cancer - page 182
- Epidemiology - page 182
- Current treatment options - page 184
- Unmet needs - page 185
- Pipeline - page 186
- Abgenix/Amgen's Panitumumab (ABX-EGF) - page 188
- ADVENTRX Pharmaceuticals' CoFactor (ANX-510) - page 190
- Pro-Pharmaceuticals' Davanat - page 192
- Novartis/Schering AG's PTK-787 (vatalanib) - page 193
- Datamonitor forecasts - page 194
- Datamonitor drug assessment summary - page 196
- CHAPTER 7 GASTRIC CANCER - page 198
- Overview - page 198
- Definition of gastric cancer - page 198
- Adenocarcinomas have the highest incidence - page 199
- Epidemiology of gastric cancer - page 199
- Despite declining incidence, gastric cancer remains a health burden - page 201
- The incidence of gastric cancer is highest in Asia, Eastern Europe and South America - page 202
- Current treatment options - page 202
- Survival of patients varies by geographical location and stage - page 202
- Surgery - page 203
- Aim is to remove involved stomach but preserve continuity - page 203
- Neoadjuvant therapy - page 203
- The incorporation of neoadjuvant therapy into treatment guidelines is likely to be the next major change to occur in the gastric cancer treatment market - page 203
- Adjuvant therapy - page 204
- Despite finding a place in standard treatment, many controversies over the use of adjuvant therapy still exist - page 204
- First-line chemotherapy for advanced disease - page 205
- Chemotherapy should be offered to those metastatic patients with a good performance status - page 205
- The ECF regimen (epirubicin, cisplatin, 5-fluorouracil) is now the current standard for the first-line treatment of advanced gastric cancer - page 205
- The recent approval of Sanofi-Aventis Taxotere in first-line therapy represents the first formal FDA approval in over a decade - page 205
- No established second-line chemotherapy regimen exists for advanced gastric cancer - page 206
- Unmet needs - page 207
- Pipeline analysis - page 207
- Camptosar (irinotecan), Daiichi/Yakult/Pfizer - page 208
- Camptosar did not demonstrate survival benefit in the first-line setting - page 209
- Camptosar may be integrated into second-line chemotherapy following results of an ongoing Phase III clinical trial - page 209
- Ellence (epirubicin), Pfizer - page 210
- Results of the Phase III MAGIC trial suggest role of neoadjuvant chemotherapy in gastric cancer - page 210
- Eloxatin (oxaliplatin), Sanofi-Aventis - page 212
- The REAL-2 trial is aiming to update the ECF regimen by using Eloxatin and Xeloda - page 213
- Xeloda (capecitabine), Roche - page 214
- Herceptin (trastuzumab), Genentech/Roche - page 215
- Phase III trial results eagerly anticipated to assess the full viability of Herceptin in HER2-positive gastric cancer - page 215
- Pipeline drug sales forecasts to 2016 - page 218
- Datamonitor drug assessment summary - page 219
- Camptosar (irinotecan), Daiichi/Yakult/Pfizer - page 208
- CHAPTER 8 HEAD AND NECK CANCER - page 221
- Overview - page 221
- Definition of head and neck cancer - page 221
- Epidemiology - page 222
- Head and neck cancer is the most frequently reported neoplasm in central Asia - page 222
- Cancer of the oral cavity has the highest incidence - page 223
- Forecast incidence of cancer of the nasopharynx - page 224
- Forecast incidence of cancer of the larynx - page 224
- Estimated incidence of cancer of the pharynx - page 225
- Cumulative estimated incidence of cancer of the oral cavity, larynx, pharynx, nasopharynx and 'other' pharynx - page 225
- Incidence is higher in countries with high alcohol consumption and smoking rates - page 226
- Demographics of head and neck cancer is changing - page 227
- Current treatment options - page 227
- Approval of Erbitux signals the first change in therapy for decades - page 228
- Approval of Erbitux in the first-line setting - page 228
- Approval in the recurrent and/or metastatic disease - page 229
- Approval of Erbitux signals the first change in therapy for decades - page 228
- Unmet needs - page 229
- Pipeline analysis - page 230
- Tirazone (tirapazamine), Sanofi-Aventis - page 232
- Additional Phase III trials are being initiated despite lack of data from existing trials - page 232
- Results of Phase III trial expected at the end of 2006 - page 232
- Randomized Phase II trial generated positive results forming the basis for Phase III examination - page 233
- Substudy results of Phase II trial confirm Tirazone targets hypoxic tumor cells - page 233
- Mature study results of Phase II trial does not increase survival support or earlier results - page 234
- Phase III trial results are required to confirm efficacy of Tirazone in advanced head and neck cancer - page 235
- Taxotere (docetaxel), Sanofi-Aventis - page 235
- Neoadjuvant Taxotere extends survival in head and neck cancer - page 236
- Filing to the FDA and EMEA for neoadjuvant Taxotere in head and neck cancer is ongoing - page 237
- Taxotere in head and neck cancer represents a lucrative opportunity for Sanofi-Aventis - page 237
- The biggest threat to Taxotere sales is patent expiry in 2010 - page 237
- Iressa (gefitinib), AstraZeneca - page 237
- Iressa demonstrates activity in head and neck cancer - page 238
- Phase II trials have demonstrated clinical benefit in 45% of patients with recurrent SCCHN - page 238
- Can Iressa overcome its bad publicity and secure its place in the head and neck market - page 239
- Pipeline drug sales forecasts to 2016 - page 240
- Datamonitor drug assessment summary - page 242
- Tirazone (tirapazamine), Sanofi-Aventis - page 232
- CHAPTER 9 HEPATOCELLULAR CARCINOMA - page 244
- Overview - page 244
- Definition of hepatocellular carcinoma - page 244
- Epidemiology - page 245
- HCC has well-defined risk factors - page 245
- Incidence of HCC has increased dramatically in western countries - page 245
- Full effects of HBV vaccination programs will not be observed for another 10-15 years - page 246
- Datamonitor forecasts of HCC in the seven major markets - page 246
- Treatment options - page 249
- Compromised liver function restricts treatment options - page 249
- Three treatment modalities prevail - page 249
- HCC is the only tumor for which transplantation plays a role - page 250
- Recurrence can occur after transplant - page 251
- Surgery is limited to only 5-15% of patients - page 251
- Systemic chemotherapy is of limited use in HCC - page 252
- Despite limited activity doxorubicin is the most frequently employed cytotoxic - page 253
- Recent randomized Phase III trial confirms doxorubicin as most effective agent in HCC - page 254
- Variability in response rates with doxorubicin may be a reflection of trial design - page 255
- Novel local delivery techniques in HCC - page 255
- Radiofrequency ablation destroys the tumor while sparing the liver - page 256
- Radiofrequency ablation is comparable to surgery in selected patients - page 256
- High rate of recurrence with RFA highlights need for supplementary agents - page 257
- Percutaneous ethanol injection - page 257
- Cryoablation - page 258
- Chemoembolization (TACE) delivers chemotherapy direct to tumor - page 258
- TACE is most effective in small tumors - page 260
- Unmet needs - page 261
- Pipeline analysis - page 262
- Bayer/Onyx's Nexavar (sorafenib) - page 263
- First-in-class agent demonstrates impressive activity in HCC - page 263
- Bayer complete enrollment of Phase III trial in May 2006 - page 264
- Phase II trials suggest doubling of median survival compared to doxorubicin - page 264
- Nexavar in HCC - page 265
- Nexavar does not have overlapping toxicities with doxorubicin - page 265
- First-to-market status and collaboration will ensure Nexavar is the leading multi-kinase inhibitor - page 266
- Eximias' Thymitaq (nolatrexed dihydrochloride, ZX337) - page 266
- Development put on hold following final Phase III trial results - page 266
- Interim safety analysis of the trial was positive - page 266
- Thymitaq's future is uncertain - page 268
- Eximias' lack of marketing and sales experience would further hinder Thymitaq's uptake - page 269
- Thalidomide (thalidomide), TTY BioPharm - page 269
- A phase III trial examining thalidomide in HCC is ongoing - page 270
- Phase II trial results do not support the use of thalidomide in HCC - page 270
- Additional Phase II trial does not support use of thalidomide in HCC - page 270
- Response in some patients may be due to etiology - page 271
- Thalidomide unlikely to make its mark on the HCC market - page 272
- Pipeline drug sales forecasts to 2016 - page 273
- Datamonitor drug assessment summary - page 275
- Bayer/Onyx's Nexavar (sorafenib) - page 263
- Overview - page 244
- CHAPTER 10 NON-SMALL CELL LUNG CANCER - page 277
- Disease overview - page 277
- Epidemiology of NSCLC - page 277
- The NSCLC death rate now exceeds that of breast, prostate and colon cancers combined - page 277
- Treatment options - page 282
- Surgical resection offers the greatest potential for cure - page 282
- Radiation therapy is considered a potential cure for Stage I-II patients - page 282
- Chemotherapy plays a major role for the majority of NSCLC patients - page 283
- First-line cytotoxics: 30 years on, they still remain the forefront treatment of advanced NSCLC - page 283
- Second- and third-line NSCLC: drug options have expanded over the past decade - page 284
- NCCN recommends, yet to be approved, Avastin as a first-line treatment - page 285
- Neoadjuvant and adjuvant chemotherapy is used to destroy micrometastases - page 287
- Adjuvant chemotherapy: platinum-based doublets offer limited survival benefit - page 287
- Neoadjuvant chemotherapy is undergoing investigation in Stage IB-II patients - page 287
- Thirty years on: the optimal drug regimen remains unknown and survival poor - page 288
- Unmet needs in NSCLC are significant - page 289
- Five-year survival rates have failed to improve despite advances in drug development - page 289
- A first-line agent with reduced toxicity is urgently needed - page 290
- Despite constituting around 65% of all NSCLC patients, suitable therapeutics for the elderly remain elusive - page 291
- Effective second-line therapy needed for half of all chemotherapeutically treated patients - page 292
- Bronchioalveolar carcinoma and adenocarcinoma patients are underserved - page 292
- Stage IIIA patients are a missed commercial opportunity - page 292
- Adjuvant and neoadjuvant treatments need defining and improving - page 293
- Development of a chemopreventative has considerable interest among oncologists - page 293
- Pipeline analysis - page 294
- Genentech/Roche's Avastin (bevacizumab) - page 297
- Avastin is the first anti-angiogenic agent to gain approval - page 297
- Positive clinical trial data announced at ASCO 2004 and 2005 - page 298
- Avastin first-line Phase II trial data show an almost 18-month survival duration - page 299
- Avastin's first-line Phase III trial demonstrates 61% improvement of progression-free survival - page 300
- Second-line Avastin Phase I/II trial holds promise - page 301
- Avastin's patient potential is 40-50% of all advanced NSCLC patients - page 302
- Genentech/Roche's experience must be used to persuade Avastin is safe - page 303
- OXiGENE's Combretastatin Combretastatin (CA4P) - page 304
- Clinical data demonstrate Combretastatin to prolong survival to almost a year - page 304
- Yantai Medgenn's Endostar (YH-16) - page 305
- Endostar's Phase III data shows significant clinical benefit - page 305
- ImClone/Bristol-Myers Squibb/Merck KGaA's Erbitux (cetuximab) - page 306
- Erbitux, the EGFR monoclonal antibody, is involved in numerous ongoing NSCLC trials - page 306
- Clinical trial data - page 308
- First-line Phase II Erbitux trials show interesting data for the under 60 age group of NSCLC patients - page 309
- Erbitux second-line Phase II studies have examined both monotherapy and doublet therapy - page 310
- Erbitux adjuvant therapy Phase II data are limited - page 311
- Erbitux has an impressive patient potential... - page 311
- ...but this could be negatively impacted by the agent's price - page 312
- Novelos' Glutoxim (NOV-002) - page 313
- Glutoxim is a stabilized formulation of oxidized glutathione - page 313
- Phase I/II data is limited because of inadequate patient enrollment - page 314
- If Phase III data repeat the 80% improvement over standard cytotoxics then Glutoxim could enjoy a significant patient potential - page 315
- Novelos' lack of commercialization partner could see Glutoxim struggle on the NSCLC market - page 315
- AEterna Zentaris' Neovastat (AE-941) - page 316
- Neovastat is a compound from shark cartilage with multiple mechanisms of action - page 316
- NCI's Data and Safety Monitoring Board terminates Phase III patient recruitment - page 316
- AstraZeneca's Zactima (vandetanib; ZD6474) - page 317
- Zactima Phase II trials still continue - page 317
- Onyx Pharmaceuticals/Bayer's Nexavar (sorafenib) - page 318
- Nexavar is the first oral multi-tyrosine kinase inhibitor to reach the market - page 318
- Clinical trial data - page 319
- Nexavar's results from second-line NSCLC specific clinical trials are encouraging - page 320
- Nexavar NSCLC non-specific second-line clinical trial demonstrates disease stabilization of over six months in 16% of patients - page 321
- Nexavar's patient potential could reach almost 53,000 advanced patients in today's seven major markets - page 321
- The fast progression of Nexavar is impressive - page 321
- Coley Pharmaceuticals/Pfizer's ProMune (CpG-7909) - page 322
- ProMune is the first targeted toll-like receptor agonist - page 322
- ProMune Phase II data find immunotherapeutic extends survival to almost one year - page 323
- ProMune has a good patient potential thanks to a favorable dosing regimen - page 324
- Pfizer partnership will aid Coley in the commercialization of ProMune - page 324
- Telik's Telcyta (TLK286, canfosfamide) - page 324
- Telcyta: a small molecule prodrug with dual antitumor activity developed using Telcyta's TRAP technology - page 324
- Clinical trial data - page 326
- First-line Telcyta interim results show promise - page 327
- Second- and third-line Telcyta results show co-administration with cytotoxics is required - page 327
- Telik was unfortunate to use Iressa as a comparator in Telcyta's ASSIST-2 trial - page 328
- Telik may struggle to commercialize Telcyta - page 329
- Pierre Fabre/Bristol-Myers Squibb's Javlor (vinflunine) - page 329
- Javlor is a vinca alkaloid undergoing European Phase III NSCLC trials - page 329
- Clinical trial data - page 329
- First-line results improve disease control by 77% for Stage IIB, III and IV NSCLC patients - page 330
- Second-line trial demonstrates encouraging survival data - page 331
- Javlor patient potential is too early to determine - page 331
- Pierre Fabre was wise to choose Bristol-Myers Squibb over GlaxoSmithKline as Javlor's marketing partner - page 332
- Sonus' Tocosol (paclitaxel) - page 332
- Tocosol is a vitamin-E based formulation of paclitaxel - page 332
- Clinical trial data - page 334
- Tocosol has a favorable toxicity profile - page 335
- Tocosol's true patient potential is difficult to assess because of a dearth of survival data - page 335
- Schering AG could raise Tocosol's profile - page 335
- IVAX's Xorane (paclitaxel poliglumex) - page 336
- Xorane: an oral cremophor formulation of paclitaxel - page 336
- Phase II data show Xyotax leads to a six-month survival period - page 336
- Xorane's patient potential is limited because of targeting PS2 NSCLC patients only - page 338
- The ongoing merger of IVAX and Teva could prove vital for Xyotax's future - page 338
- Cell Therapeutics' Xyotax (polyglutamate paclitaxel) - page 338
- Drug overview - page 338
- Clinical trials - page 340
- STELLAR studies prove exciting news for advanced, premenopausal poor performance NSCLC women - page 340
- Xyotax Phase II PGT-202 data shows promise for non-PS2 patients - page 342
- A range of problems looks set to reduce Xyotax's patient potential - page 343
- Cell Therapeutics' limited presence within the EU and US could restrict Xyotax's revenues - page 344
- Pipeline drug sales forecasts to 2016 - page 344
- Avastin looks set to dominate the NSCLC market becoming a blockbuster by 2012 - page 347
- Javlor is anticipated to become the leading cytotoxic of those in late-stage NSCLC development - page 348
- Difficulties in the commercialization of immunotherapies account for low sales forecasts - page 348
- Datamonitor's Drug assessment summary - page 349
- Molecular targeted therapies drug assessment finds Avastin compares well to Tarceva and is of relatively low commercial risk - page 349
- Datamonitor's drug assessment model shows Xorane and Javlor have similar research, clinical and commercial potential - page 352
- Immunotherapy drug assessments - page 354
- Genentech/Roche's Avastin (bevacizumab) - page 297
- CHAPTER 11 OVARIAN CANCER - page 356
- Overview - page 356
- Definition of ovarian cancer - page 356
- Epidemiology - page 357
- Unmet needs - page 357
- Current treatment options - page 358
- Pipeline - page 360
- Xyotax (polyglutamate paclitaxel); Cell Therapeutics - page 362
- Impressive results but need to be replicated in Phase III trial - page 362
- Effect on QoL - page 363
- Sufficient advantages for reformulated paclitaxel? - page 363
- Patupilone (epothilone B); Novartis - page 364
- Limited potential for patupilone - page 364
- More epothilone agents on the horizon - page 365
- Unither Therapeutics/ViRexx - OvaRex (oregovomab) - page 365
- Primary endpoint failure will hurt the drug - page 366
- Insufficient marketing capacity and capability - page 366
- Telcyta (TLK286); Telik - page 366
- Penetrating the second- and third-line market - page 367
- Partner needed for Telcyta - page 368
- Thalomid (thalidomide); Celgene - page 368
- Lack of Celgene support? - page 369
- Stigma of thalidomide - page 369
- Avastin (bevacizumab); Genentech/Roche - page 370
- Confidence transferred to ovarian cancer - page 370
- Cost will be a problem for Avastin - page 371
- Tarceva (erlotinib); Genentech/Roche/OSI - page 372
- Winning streak for Genentech/Roche? - page 372
- Yondelis (trabectedin); PharmaMar - page 373
- Unlikely to change the treatment paradigm - page 373
- More potential with combination therapy? - page 374
- Phenoxodiol; Marshall Edwards - page 374
- Toxicity will be the key factor for phenoxodiol - page 374
- Sanofi-Aventis as a marketing partner? - page 375
- Datamonitor forecasts - page 375
- Datamonitor's drug assessment summary - page 379
- Xyotax (polyglutamate paclitaxel); Cell Therapeutics - page 362
- CHAPTER 12 PANCREATIC CANCER - page 381
- Overview - page 381
- Definition of pancreatic cancer - page 381
- Epidemiology - page 381
- Current treatment options - page 383
- Surgery is employed for early-stage pancreatic cancer - page 384
- Gemcitabine remains the cornerstone of first-line treatment - page 384
- FDA approves first agent in pancreatic cancer in nine years - page 384
- Unmet needs - page 385
- Pipeline - page 386
- Avastin (Bevacizumab), Genentech/Roche - page 388
- Phase III trial fails to demonstrate survival benefit - page 388
- Phase II trial results demonstrate activity in combination with gemcitabine - page 388
- Increased risk of bleeding may deter prescribing in this setting - page 389
- Genentech/Roche's presence in the oncology arena will confer significant marketing push - page 389
- Eloxatin (oxaliplatin) Sanofi-Aventis - page 390
- Eloxatin does not confer statistically significant survival benefit in pancreatic cancer - page 390
- Phase III trials confer clinical benefit but not overall survival - page 391
- Eloxatin will need to realize survival benefit to achieve significant uptake - page 392
- Erbitux (cetuximab), ImClone/Merck KGaA/BMS - page 392
- Phase II trials demonstrate activity in combination with Erbitux in pancreatic cancer - page 392
- Approval likely if Phase III trial results mimic Phase II activity - page 393
- BMS' and Merck's presence in the oncology market will ensure significant market penetration - page 393
- Economic restraints on healthcare systems may limit uptake - page 394
- Glufosfamide; Threshold - page 394
- Independent Data Monitoring Committee recommend continuation of the Phase III trial - page 394
- Phase II trial demonstrated activity in advanced pancreatic cancer - page 395
- Threshold has no marketed products - page 395
- Pipeline drug sales forecasts to 2016 - page 395
- Datamonitor drug assessment summary - page 398
- Avastin (Bevacizumab), Genentech/Roche - page 388
- CHAPTER 13 PROSTATE CANCER - page 400
- Overview - page 400
- Definition of prostate cancer - page 400
- Epidemiology - page 401
- Unmet needs - page 403
- Current treatment options - page 403
- Pipeline - page 404
- Satraplatin; GPC Biotech - page 406
- Oral availability will be popular - page 406
- Potential in first- and second-line treatment - page 406
- Limited second-line market size - page 407
- Possibility of alliance in the US - page 407
- Avastin (bevacizumab); Genentech/Roche - page 407
- Promising results in Phase II - page 408
- Confidence likely to be transferred to prostate cancer - page 408
- Will Avastin's toxicity limit its uptake? - page 408
- Cost may be a limiting factor for Avastin - page 409
- Degarelix; Ferring/Astellas - page 410
- Lack of testosterone flare - page 410
- Lupron and Zoladex stand in the way - page 410
- Need to overcome skepticism - page 411
- DN-101 (calcitriol); Novacea - page 411
- High awareness but need for marketing partner - page 412
- Need for Phase III data - page 412
- Xinlay (atrasentan); Abbott - page 413
- Negative recommendation by ODAC - page 413
- AstraZeneca's pipeline drug on its heels - page 414
- Datamonitor forecasts - page 415
- Datamonitor's drug assessment summary - page 417
- Satraplatin; GPC Biotech - page 406
- CHAPTER 14 RENAL CELL CARCINOMA - page 419
- Overview - page 419
- Definition of renal cell carcinoma - page 419
- Approximately one-third of patients have metastatic disease at presentation - page 420
- Epidemiology - page 421
- Incidence of kidney cancer is increasing at a rate of 2-4% per year - page 421
- Current treatment options - page 423
- Surgery remains the cornerstone of RCC treatment - page 423
- RCC tends to be radiotherapy- and chemotherapy-resistant - page 424
- Radiofrequency ablation can be as successful as surgery for small tumors - page 424
- Immunotherapy was previously the standard for metastatic RCC - page 425
- Onyx Pharmaceuticals/Bayer's Nexavar (sorafenib), the first drug in over a decade to be approved for kidney cancer - page 425
- Nexavar doubles progression-free survival to 24 weeks - page 426
- Pfizer's Sutent (sunitinib) approved in January 2006 - page 427
- New Phase III trial results suggest that Sutent should become the first-line standard of care in RCC - page 427
- Phase II studies show second-line Sutent delays disease progression by 8.7 months - page 427
- Sutent has an acceptable toxicity profile, with most adverse effects mild in nature - page 428
- Unmet needs - page 429
- Pipeline - page 429
- Wyeth's Temsirolimus (CCI-779) - page 431
- Promising Phase III results reported at ASCO 2006 - page 431
- Phase II trial results demonstrate objective response rate of 7% - page 432
- The focus of poor-risk patients may eventually expedite temsirolimus's expansion within RCC - page 433
- Wyeth has some presence in the oncology market - page 433
- Wilex AG/Esteve SA's Rencarex (WX-G250) - page 434
- Phase III clinical trials target adjuvant non-metastatic RCC patients - page 434
- Phase II Rencarex data show improvement in median survival to 15 months - page 435
- Lack of Phase II data in the adjuvant setting raises questions regarding Phase III design - page 436
- Wilex has limited sales and marketing to drive sales forward - page 437
- Genentech/Roche's Avastin (bevacizumab) - page 437
- Phase III trial examining Avastin in metastatic RCC - page 437
- Phase II monotherapy study shows Avastin improves progression-free survival to 4.8 months - page 438
- Updated results of a Phase II trial combining Tarceva and Avastin demonstrate significant activity in recurrent RCC - page 438
- Initial Phase II study suggested that the addition of Genentech/Roche/OSI's Tarceva (erlotinib) to Avastin may improve survival - page 439
- Phase II trial results with Tarceva and Avastin are conflicting - page 439
- Wyeth's Temsirolimus (CCI-779) - page 431
- Datamonitor forecasts - page 440
- Datamonitor drug assessment summary - page 441
- APPENDIX A - page 443
- Methodology - page 443
- Datamonitor forecast methodology - page 443
- Epidemiology forecasts - page 443
- Product forecasts - page 443
- Datamonitor drug assessment summary - page 443
- Datamonitor forecast methodology - page 443
- References - page 447
- Methodology - page 443
- APPENDIX B - page 494
- About Datamonitor - page 494
- About Datamonitor Healthcare - page 494
- Datamonitor Healthcare's therapy area capabilities - page 495
- About the Oncology analysis team - page 495
- DISCLAIMER - page 497
- About Datamonitor - page 494
- List of Tables
- Table 1: Incidence of 11 tumor types in the seven major markets, 2006 - page 10
- Table 2: Incidence of 11 tumor types in the seven major markets, 2006 - page 10
- Table 3: Sales forecasts for Phase III pipeline oncology drugs ($m), 2006-2016 (1 of 3) - page 13
- Table 4: Sales forecasts for Phase III pipeline oncology drugs ($m), 2006-2016 (2 of 3) - page 14
- Table 5: Sales forecasts for Phase III pipeline oncology drugs ($m), 2006-2016 (3 of 3) - page 15
- Table 6: Drugs in Phase II and III development for 11 tumor types by indication, 2006 - page 49
- Table 7: Drugs in Phase II and III development for 11 tumor types by drug class, 2006 - page 51
- Table 8: Cytotoxic agents in Phase II and III development across 11 tumor types, 2006 - page 53
- Table 9: Antihormonal agents in Phase II and III development in breast and prostate cancer, 2006 - page 56
- Table 10: Signal transduction inhibitors in Phase II and III development across 11 tumor types, 2006 - page 57
- Table 11: Angiogenesis inhibitors in Phase II and III development across 11 tumor types, 2006 - page 59
- Table 12: Apoptosis stimulators in Phase II and III development across 11 tumor types, 2006 - page 60
- Table 13: Immunotherapies in Phase II and III development across 11 tumor types, 2006 - page 61
- Table 14: Miscellaneous drugs in Phase II and III development across 11 tumor types, 2006 - page 62
- Table 15: Common mutations involved in tumor development - page 64
- Table 16: Crude incidence rates of female breast cancer (per 100,000 population) in the seven major markets, 2002 - page 84
- Table 17: Forecast incidence of female breast cancer in the seven major markets, 2002-2016 - page 84
- Table 18: Stage-specific incidence of female breast cancer in the seven major markets, 2006 - page 85
- Table 19: NCCN adjuvant guidelines for breast cancer, 2006 - page 88
- Table 20: NCCN-recommended post-menopausal hormonal therapy options for breast cancer, 2006 - page 91
- Table 21: NCCN-recommended single-agent treatment of advanced breast cancer, 2006 - page 91
- Table 22: NCCN-recommended combination treatment of advanced breast cancer, 2006 - page 93
- Table 23: Approved dosing schedules for Herceptin, 2006 - page 94
- Table 24: Five-year relative survival rate by disease stage at diagnosis, 2006 - page 96
- Table 25: Drugs in Phase III development for breast cancer, March 2006 - page 99
- Table 26: Drugs in Phase II development for breast cancer, 2006 (1 of 3) - page 100
- Table 27: Drugs in Phase II development for breast cancer, 2006 (2 of 3) - page 101
- Table 28: Drugs in Phase II development for breast cancer, 2006 (3 of 3) - page 102
- Table 29: Ongoing Avastin breast cancer clinical trials, 2006 - page 104
- Table 30: Summary of key Avastin breast cancer clinical trials - page 105
- Table 31: E2100 Avastin breast cancer clinical trial: survival results - page 106
- Table 32: E2100 Avastin breast cancer clinical trial: toxicity results - page 106
- Table 33: Avastin plus capecitabine Phase III trial: results - page 107
- Table 34: Summary of key Advexin breast cancer clinical trials, 2006 - page 111
- Table 35: Phase II arzoxifene locally advanced/metastatic breast cancer results: efficacy - page 115
- Table 36: Tesmilifene's Phase I-II breast cancer trial results, 2006 - page 118
- Table 37: Phase III tesmilifene metastatic/recurrent breast cancer trial: efficacy results - page 120
- Table 38: Phase III tesmilifene metastatic/recurrent breast cancer trial: Grade 3-4 adverse effects of patients in either arm - page 121
- Table 39: Summary of key Tocosol paclitaxel breast cancer clinical trials, 2006 - page 124
- Table 40: Tocosol paclitaxel Phase IIB trial data, 2006 - page 126
- Table 41: Single-agent Taxotere, Taxol and Abraxane Phase III metastatic breast cancer trial data: efficacy - page 127
- Table 42: Tocosol Phase IIb trial: toxicity profile, 2006 - page 128
- Table 43: Ongoing Tykerb/Tycerb clinical trials, 2006 - page 131
- Table 44: Summary of key Tykerb/Tycerb breast cancer clinical trials, 2006 - page 132
- Table 45: Tykerb/Tycerb Phase II Herceptin-resistant metastatic breast cancer trial results (n=41) - page 135
- Table 46: Ongoing XRP-9881 breast cancer clinical trials, 2006 - page 140
- Table 47: Summary of key XRP- 9881 breast cancer clinical trials, 2006 - page 141
- Table 48: XRP-9881 Phase II efficacy data for taxane-resistant (RS) and taxane non-resistant (NRS) metastatic breast tumors - page 142
- Table 49: XRP-9881 Phase II Grade 3-4 toxicity results for taxane-resistant (RS) and non-taxane resistant (NRS) metastatic breast tumors - page 143
- Table 50: Assumptions influencing sales forecasts of breast cancer pipeline compounds, 2006 - page 145
- Table 51: Assumptions influencing sales forecasts of breast cancer pipeline compounds, 2006 - page 146
- Table 52: Sales forecasts for pipeline breast cancer drugs, 2006-2016 - page 146
- Table 53: Summary of commercial and research/clinical attractiveness of late-phase drugs for breast cancer, 2006 - page 148
- Table 54: Crude incidence rates of primary brain cancer (per 100,000 population) by gender in the seven major markets, 2002 - page 152
- Table 55: Estimated incidence of brain cancer in the seven major markets, 2002-2016 - page 152
- Table 56: Estimated incidence of glioma in the seven major markets, 2002-2016 - page 153
- Figure 32: Distribution of primary brain and CNS gliomas, 2006 - page 154
- Table 57: Estimated incidence of glioblastoma multiforme in the seven major markets, 2002-2016 - page 154
- Table 58: EORTC Phase III trial results supporting FDA approval of temozolomide for newly diagnosed glioblastoma, 2006 - page 157
- Table 59: Methylated MGMT confers better prognosis for glioblastoma patients, 2005 - page 159
- Table 60: Drugs in Phase III development for glioma, March 2006 (cont'd) - page 160
- Table 61: Drugs in Phase II development for glioma, March 2006 (cont'd) - page 161
- Table 62: Drugs in Phase II development for glioma, March 2006 (cont'd) - page 162
- Table 63: Phase II trial results for enzastaurin in patients with recurrent high-grade gliomas - page 164
- Table 64: Intratumoral bleeds in patients on enzastaurin may be associated with anticoagulation therapy - page 165
- Table 65: Comparison of peritumoral delivery and intratumoral delivery - page 171
- Table 66: Assumptions influencing sales forecasts of brain cancer pipeline compounds - page 178
- Table 67: Sales forecasts for pipeline glioma drugs, 2006-2016 - page 179
- Table 68: Summary of commercial and research/clinical attractiveness of late-phase drugs for glioma, 2006 - page 180
- Table 69: Crude incidence rates of colorectal cancer by gender (per 100,000 population) in the seven major pharmaceutical markets, 2002 - page 183
- Table 70: Incidence of colorectal cancer in the seven major pharmaceutical markets, 2002-2016 - page 183
- Table 71: Late-stage pipeline compounds for colorectal cancer, 2006 - page 186
- Table 72: Phase II compounds for colorectal cancer, 2006 - page 187
- Table 73: Ongoing clinical trials involving panitumumab in metastatic colorectal cancer, 2006 - page 189
- Table 74: Ongoing clinical trials involving CoFactor in metastatic colorectal cancer, 2006 - page 191
- Table 75: Ongoing clinical trials involving Davanat in metastatic colorectal cancer, 2006 - page 192
- Table 76: Assumptions influencing sales forecasts of colorectal cancer pipeline compounds - page 194
- Table 77: Key colorectal cancer drugs pipeline miscellaneous sales forecasts, 2006-2016 ($m) - page 195
- Table 78: Summary of commercial and research/clinical attractiveness of late-phase drugs for colorectal cancer, 2006 - page 196
- Table 79: Proportion of different pathologies of gastric tumor - page 199
- Table 80: Crude incidence rates of gastric cancer by gender (per 100,000 population) in the seven major pharmaceutical markets, 2002 - page 200
- Table 81: Estimated incidence of gastric cancer in the seven major pharmaceutical markets, 2002-2016 - page 200
- Table 82: Drugs in Phase
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