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ABOUT DATAMONITOR HEALTHCARE 2About the Oncology pharmaceutical analysis team 2CHAPTER 1 EXECUTIVE SUMMARY 3Scope of the analysis 3Datamonitor insight into the chronic leukemias market 3Datamonitor insight into the CLL market 3Datamonitor insight into the CML market 4Contributing experts 5Related reports 6Upcoming reports 6CHAPTER 2 INTRODUCTION AND SCOPE 8Coverage of the Stakeholder Insight Survey 8Disease definition and epidemiology 8Segmentation of the chronic leukemia population 8Current drug treatment practice for CLL and CML 8Key unmet needs within the CLL and CML market 9Potential of pipeline drugs for CLL and CML 9CHAPTER 3 COUNTRY TREATMENT TREES 10Introduction 10CLL country treatment trees 10US 12Japan 15France 18Germany 21Italy 24Spain 27UK 30CML country treatment trees 33US 35Japan 37France 39Germany 41Italy 43Spain 45UK 47CHAPTER 4 CLL: DISEASE OVERVIEW, EPIDEMIOLOGY AND PATIENT SEGMENTATION 49Introduction 49CLL is an incurable disease characterized by an accumulation of mature B-lymphocytes 49Most CLL patients are asymptomatic at presentation 49Etiology of CLL is poorly understood 50Epidemiology of CLL 51Incidence of leukemia subtypes in the seven major markets 51CLL is the most commonly diagnosed subtype of leukemia in the seven major markets 51Forecast incidence of CLL in the seven major markets, 2008-2017 53Age distribution of CLL incidence rates 55Segmentation of the CLL population 57The Rai and Binet staging systems 57US and Japan physicians most commonly use Rai system; EU physicians most commonly use Binet system 57Disease stage at presentation 59The majority of CLL patients have early-stage disease at diagnosis 59Identification of high-risk patients 63CHAPTER 5 CLL: TREATMENT TRENDS AND TREATMENT OUTCOMES 65Overview of CLL treatment options 65Summary of agents used to treat CLL 65Key clinical trial data 67Ribomustin/Treanda (bendamustine; Astellas/Cephalon) 67Chlorambucil 68Fludarabine 69Campath (alemtuzumab; Takeda/Genzyme/Bayer Schering) 70Rituxan/MabThera (rituximab; Biogen Idec/Genentech/Roche/Zenyaku Kogyo) 74Summary of CLL treatment strategies 79Physicians commonly initiate first-line treatment after a period of observation 79First-line treatment choices depend on several factors 80Treatment choices for relapsed CLL depend on outcome for first-line therapy 80Treatment of refractory CLL is challenging 81Percentage of patients receiving treatment 82Rai Stage 0 82The majority of Rai Stage 0 patients do not receive anti-cancer drug therapy 83Rai Stage I-II 84Over half of Rai Stage I-II patients receive anti-cancer treatment 85Rai Stage III-IV 85The majority of Rai Stage III-IV patients receive treatment immediately after diagnosis 87Duration of observation 88Duration of observation before initiation of treatment depends strongly on disease stage 89First-line treatment trends 90Use of first-line regimens by Rai Stage 90Rai Stage 0 90Rai Stage I-II 94Rai Stage III-IV 98There is no firmly established stand-of-care for first-line treatment of CLL 102Off-label use of Rituxan-containing regimens is more common in the US than in the 5EU and Japan 104Toxicity concerns, skepticism over the Phase III trial and limited awareness of suitable candidates for treatment have limited uptake of Campath for first-line CLL 105Use of first-line regimens by country 107US 108Japan 109France 112Germany 114Italy 116Spain 118UK 120First-line treatment outcomes 122Response criteria 122Rai Stage 0 12250% of treated Rai Stage 0 patients achieve a complete remission 125Rai Stage I-II 126CR rates for Rai Stage I-II correlate with the use of FCR 128Rai Stage III-IV 129Higher remission rates for Rai Stage III-IV CLL in the US correlate with commonplace use of FCR 131Second-line treatment trends 132Percentage of patients progressing to second-line therapy 132The majority of late-stage CLL patients progress to a second-line regimen 133Second-line regimens 134More than half of second-line patients receive a Rituxan-containing regimen 138Toxicity profile and low efficacy in some patients have restricted second-line uptake of Campath to modest levels 139Second-line treatment trends by regimen prescribed initially 140A high percentage of physicians use second-line Campath after FCR or FC 141Second-line treatment outcomes 142Modest treatment outcomes highlight the need for more effective second-line therapy 142Third-line treatment trends 145Percentage of patients progressing to third-line therapy 145Approximately half of second-line patients progress to a third-line regimen 146Third-line regimens 146Single-agent Campath is the most commonly used third-line regimen, although Rituxan-based regimens are more commonly used overall 150Third-line treatment outcomes 151Over 40% of patients do not achieve a partial remission or complete remission after third-line therapy 151Further lines of therapy 153The majority of third-line patients receive no further treatment 153CHAPTER 6 CLL: PRESCRIBING INFLUENCES AND BRAND ASSESSMENT 155Factors influencing prescribing decisions in CLL 155Efficacy is the most important prescribing influence for CLL 155Physician perception of approved and late-phase pipeline CLL therapies 156Physicians perceive Campath to be the most effective CLL drug 158Toxicity and safety for extended use is rated highest for Rituxan 159Rituxan scores higher than Campath for most other attributes 159Brand map overview of attributes and drug perception in CLL 159Interpreting a brand map 159CHAPTER 7 CLL: UNMET NEEDS 162Ranking of unmet needs in CLL 162Curative treatment is the biggest unmet need in CLL 162CHAPTER 8 CLL: LATE-PHASE PIPELINE OVERVIEW 164Products in Phase III development for CLL 164Genasense (Oblimersen; Genta) 164Drug overview 164Key historical events 165Datamonitor comments 167Approval of Genasense is looking increasingly unlikely 167Termination of agreement with Sanofi-Aventis is a major setback for Genta 168Lumiliximab (Anti-CD23 MAb; Biogen Idec) 168Drug overview 168Key historical events 169Clinical trial data 170The addition of lumiliximab to the FCR regimen may produce a higher response rate without additional toxicity 170Datamonitor comments 173Lumiliximab on course to become an established addition to the standard treatment for CLL 173Biogen Idec should look to investigate Lumiliximab as a maintenance therapy 174Ofatumumab (HuMax-CD20; Genmab/GlaxoSmithKline) 175Drug overview 175Genmab hoping ofatumumab will demonstrate a preferred efficacy profile over Rituxan in the clinic 175Key historical events 176Clinical trial data 177Ofatumumab receives Fast Track status for CLL and enters a Phase III trial 178Datamonitor comments 179Targeting underserved CLL patients may enhance ofatumumab's uptake in the market 179CHAPTER 9 CML: DISEASE OVERVIEW, EPIDEMIOLOGY AND PATIENT SEGMENTATION 181Introduction 181CML is characterized by a single genetic aberration 181CML patients are commonly asymptomatic at presentation 183Etiology of CML is unknown 183Epidemiology of CML 184Incidence of leukemia subtypes in the seven major markets 184CML is the third most commonly diagnosed subtype of leukemia in the seven major markets 184Forecast incidence of CML in the seven major markets, 2008-2017 187Age distribution of CML incidence rates 189The incidence rate of CML increases with age 189Segmentation of the CML population 191CML has a triphasic or biphasic disease course 191Disease stage at presentation 193The majority of CML patients present with chronic phase disease 193CHAPTER 10 CML: TREATMENT TRENDS AND TREATMENT OUTCOMES 195Overview of CML treatment options 195Summary of agents used to treat CML 195Definition of CML treatment outcomes 196Key CML clinical trial data 196Gleevec (imatinib; Novartis) 196Sprycel (dasatinib; Bristol-Myers Squibb) 199Tasigna (nilotinib; Novartis) 205Summary of CML treatment strategies 209Gleevec is standard-of-care for first-line chronic phase CML but there is no firm consensus for accelerated phase or blast crisis patients 209Options for Gleevec resistance include increasing the dose of Gleevec, switching to a second-generation TKI and stem cell transplantation 210Treatment trends for chronic phase CML first-line therapy 211Regimens 211Gleevec is the firmly established standard-of-care across all seven major markets for first-line chronic phase CML 211Dosing 213400mg daily is by far the most-commonly used dose used for first-line Gleevec in chronic phase CML 213First-line therapy treatment outcomes 215Over 25% of patients who achieve complete response eventually show secondary Gleevec-resistance 217Treatment trends for Gleevec resistance 221Primary Gleevec resistance 221Increasing the Gleevec dose is the most commonly used treatment approach for primary Gleevec resistance 221Secondary Gleevec resistance 223Switching to Sprycel or Tasigna is common for secondary Gleevec resistance 224Use of cytogenetic testing correlates with switching from Gleevec 225Sprycel's first-to-market advantage gives it higher market penetration than Tasigna 227Treatment trends for accelerated phase CML 228Percentage of patients progressing to accelerated phase CML 228Regimens 229High-dose Gleevec remains more popular than switching to Sprycel or Tasigna for accelerated phase CML 229Treatment trends for blast crisis CML 233Percentage of patients progressing to blast crisis CML 233Regimens 235Commonplace use of acute leukemia-type chemotherapy regimens reduces the markets' share of tyrosine kinase inhibitors for blast crisis CML 235CHAPTER 11 CML: PRESCRIBING INFLUENCES AND BRAND ASSESSMENT 238Factors influencing prescribing decisions in CML 238Efficacy is the most important prescribing influence for CML 238Physician perception of approved and late-phase pipeline CML therapies 240Physicians find it hard to differentiate between Gleevec, Sprycel and Tasigna in terms of efficacy 241Gleevec judged to have the most favorable toxicity profile; Tasigna scores higher than Sprycel 242Cost 243Tasigna's dosing schedule is considered less convenient than Gleevec and Sprycel 244Future-based scenarios in the CML market 245Physicians are undecided over which second-generation tyrosine kinase inhibitor will become the most popular 245Tasigna and Sprycel are likely to achieve increased uptake in the first-line but may not displace Gleevec as standard of care 246Brand map overview of attributes and drug perception in CML 247Interpreting a brand map 247CHAPTER 12 CML: UNMET NEEDS 249Ranking of unmet needs in CML 249Blast crisis is the greatest area of unmet need in CML but may not be the most commercially attractive 249Gleevec resistance remains an area of high unmet need 250CHAPTER 13 CML: LATE-PHASE PIPELINE OVERVIEW 253Products in Phase III development for CML 253Bosutinib (SKI-606; Wyeth) 254Drug overview 254Key historical events 254Clinical trial data 255Bosutinib Phase II results in Gleevec-resistant/intolerant chronic phase CML 255Bosutinib Phase II results in Gleevec-resistant/intolerant accelerated phase and blast crisis CML and Ph+ ALL 257Datamonitor comments 259Like the other tyrosine kinase inhibitors, bosutinib appears ineffective in patients harboring the T315I mutation - a key driver of resistance 259Bosutinib trying to catch up with Sprycel and Tasigna in the race to replace Gleevec in the front-line setting 259Ceflatonin (Myelostat; ChemGenex Pharmaceuticals) 260Drug overview 260Key historical events 261Clinical trial data 262Ceflatonin targeting Gleevec-resistant patients 262Datamonitor comments 267Despite convincing clinical benefit, Ceflatonin will face strong competition from Sprycel and Tasigna 267BIBLIOGRAPHY 268Journal papers 268Websites 275Other 277APPENDIX A 278List of tables 278List of figures 278Abbreviations 279Exchange rates 281Second-line treatment trends by regimen prescribed initially: full seven major market data 282US 282Japan 283France 284Germany 285Italy 286Spain 287UK 288Physician research methodology 289Physician sample breakdown 289US 289Japan 290France 290Germany 291Italy 292Spain 293UK 294Contributing experts 295APPENDIX B 296The survey questionnaire 296Introduction 296Section 1 - Chronic Lymphocytic Leukemia: Patient Segmentation 296Section 2 - Chronic Lymphocytic leukemia: Treatment 298Section 3 - Chronic Lymphocytic Leukemia: Product Profiles / Pipeline Products 311Section 4 - Chronic Myeloid Leukemia: Patient Segmentation 315Section 5 - Chronic Myelogenous Leukemia: Treatment 318Section 6 - Chronic Myelogenous Leukemia: Product Profiles / Pipeline Products 330Demographics 333About Datamonitor 335About Datamonitor Healthcare 335Disclaimer 337Disclaimer 337</p>>!!
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