Printer Friendly Printed from http://www.researchandmarkets.com/reports/310451 Chronic Leukemias - Curative Intent Raises The Bar Description: Introduction Recognizing that prolonging disease-free survival in chronic leukemia relies on the eradication of minimal residual disease has raised the bar for developers of novel pharmacotherapy. In meeting the more demanding success criteria and targeting innovative treatments to cohorts most likely to respond, developers should increasingly employ the use of molecular markers to guide risk stratification. Scope - Overview of chronic leukemias including epidemiology, etiology, clinical features, staging and prognostic variables - Current treatment controversies and novel therapies in the developmental pipeline - Analysis of trial data, marketing factors and commercial potential for key technologies in clinical development - Stakeholder opinions and interview transcripts based on qualitative interviews with five opinion leaders from the US and Europe Highlights Because of the heterogeneity of CLL there is a need to identify biological markers that provide a more robust and reliable prediction of patient outcomes to current and evolving treatment strategies. The identification and application of molecular markers to facilitate prognostication is becoming integral to the treatment decision-making process. The emergence of Gleevec-resistant CML, reported at rates of 4% with each year of treatment, coupled with only a 50% response rate in patients with advanced disease, indicate the need for novel, efficacious second-line treatment strategies both for patients with Gleevec-resistant chronic phase CML and for virtually all advanced stage patients. The goal for developers of novel CLL pharmacotherapy is to innovate drug treatments that can salvage patients refractory to alemtuzumab and improve on the formers toxicity while simultaneously increasing the rate and duration of minimal residual disease negativity. Reasons to Purchase - Identify opportunities for more efficacious second-line treatment strategies both for patients with Gleevec-resistant CML and advanced stage patients - Understand how future advancements in chronic leukemia prognostication have the potential to shift treatment paradigms - Assess opportunities and challenges facing innovative treatments for chronic leukemias, in particular the drive to eradicate minimal residual disease Contents: CHAPTER 1 3. Insight into the chronic leukemia market 3 Epidemiology and etiology 3 Classification and prognosis 4 Unmet needs 5 Current treatment controversies 7 Pipeline products 11 CHAPTER 2 INTODUCTION 21. The chronic leukemias are a significant source of cancer-related morbidity and mortality 21 The advent of immunotherapy is revolutionizing chronic lymphocytic leukeima (CLL) treatment 21 Chronic myeloid leukemia (CML) treatment has been revolutionized by the introduction of Novartis’s Gleevec 22 Leukemia subtypes each have their own distinctive epidemiological profile 22 Chronic lymphocytic leukemia has the greatest prevalence rate among all leukemias 30 CML has contrasting age and sex distribution 32 Chronic leukemia etiology and risk factors 33 No clear associations exist for CLL development other than familial history 33 CML contrasts to CLL with definitive associations with environmental exposures 34 Disease staging, patient symptomology and clinical course 35 Choice of CLL staging system a function of geography and historical precident 35 The Rai and Binet systems do not provide adequate information to guide treatment decisions for patients with low- to intermediate-risk CLL 37 Improved risk stratification in CLL will be necessary to mitigate heterogeneity in clinical course 38 CML is a triphasic disease with phase at diagnosis having the greatest prognostic significance. 39 CHAPTER 3 UNMET NEEDS 41. Curative treatment is still elusive in CLL 41 Advances in treatment render NCI response criteria inadequate 42 Refining treatment outcome predictions in CLL through improved prognostication 44 Using genomic aberrations to predict response to therapy 47 Developers should harness risk-straftification to improve the efficiency of drug development in CLL 48 CML unmet needs focus on Gleevec-resistance and primary refractoriness 49 Rates and duration of response to Gleevec dependent on stage of disease 49 Gleevec resistance rates reported at 4% with each year of treatment with no second-line treatment option available 50 Improved MRD eradication offers developmental opportunity 51 Durability of CCR responses to imatinib unknown 51 CHAPTER 4 CURRENT TREATMENT CONTROVERSIES 55. Shifting the CLL treatment paradigm 56 Where appropriate, inidividualized, patient-specific treatment in CLL is moving towards more curative strategies 56 The purine analogues have superceeded alkylator-based approaches in the first-line treatment of younger, healthier patients 57 Purported clinical benefit offered by combining fludarabine with alkylators is contentious 61 Treatment of fludarabine-refractory disease 61 Chemo-immunotherapy strategies drive the evolution of new CLL treatment paradigms 62 Monoclonal antibodies elicit cytotoxic effects in CLL via multiple mechanisms 63 Single agent rituximab has only modest activity in CLL 63 Combination regimens incorporating fludarabine and rituximab are becoming the new standard of care for first-line CLL treatment 66 Alemtuzumab appears pivotal to approaches for MRD eradication 68 Upcoming US Intergroup sudy will help discern between different immunotherapy approaches 74 Bone marrow transplantation (BMT) 74 Likely future role of BMT is in consolidating MRD eradication for high-risk patients 74 Results with autologous transplantation have been generally disappointing 75 Reduced-intesity transplantation offers improved efficacy and broader utility 75 Increasing risk-stratification will fragment the CLL market 77 Heightened pharmacoeconomic vigilance will place novel treatment approaches under increased scrutiny 78 CLL experts believe that targeting alemtuzumab-refractory patients is the most likely source of greater financial rewards 78 Gleevec remains the gold-standard in CML 79 Physicians unwilling to attempt treatment cessation, even in patients who achieve CCR 80 Opportunity exists for novel agent that can improves the rates of molecular remission without the need for chronic administration 81 Molecularly positive disease persists despite significant cytogenetic response rates 81 Suboptimal responders to Gleevec should be targeted by developers evaluating novel pharmacotherapy 82 Dose-escalation of Gleevec to overcome hematologic or cytogenetic resistance 82 Replacing Gleevec as first-line therapy will yield lucrative financial rewards 83 Combinatorial approaches employing Gleevec 83 Definitive role of bone marrow transplantation (BMT) in CML treatment paradigm remains ambiguous 84 CHAPTER 5 PIPELINE DRUGS 87. Immunotherapy approaches to CLL fuelled by success of rituximab and alemtuzumab 87 Passive immunotherapy with single-agent MoAb approaches have demonstrated limited activity 88 Strategies incorporating active immunotherapy are still in their relative infancy, though some early-phase clinical trail results hold promise 89 KOLs interviewed by Datamonitor express little enthusiasm for novel immunotherapy approaches 91 Ontak (denileukin difitox Ligand Pharmaceuticals) generates little excitement 91 Despite Phase III study demonstrating statistically significant improvements in ORR, Genasense (oblimersen Genta) fails to ignite KOLs imagination 92 Alvocidib (flavopiridol NCI/Sanofi-Aventis) generates renewed interest 94 Early-stage development of histone deacetylases inhibitors means that clinical potential is too early to call 97 Antiangiogenic strategies are also a focus of ongoing developmental efforts 99 Second-generation tyrosine kinase inhibitors dominate the cml pipeline 100 Two novel Bcr-Abl inhibitors are in clinical trials with promising results dasatinib and AMN107 101 Novartis and BMS sprint to the finish line in the race to commercialize a second-generation TKI 104 Multistep inhibition of signal transduction likely to be the focus of future developmental strategies 106 CHAPTER 6 OPINION LEADER TRANSCRIPTS 108. Contributing experts 108 Opinion leader 1 109 Opinion leader 2 121 Opinion leader 3 131 Opinion leader 4 143 Opinion leader 5 150 CHAPTER 7 APPENDIX 160. Bibliography 160 CML response criteria 167 List of tables 168 List of figures 170 Ordering: Order Online - visit http://www.researchandmarkets.com/reports/310451 Order by Fax - using the order form below Order By Post - print the order form below and send to Research and Markets, Guinness Centre, Taylors Lane, Dublin 8, Ireland. Page 1 of 2 Printed 29/08/2008 02:37:55 Fax Order Form To place an order via fax simply print this form, fill in the information below and fax the completed form to the number at the bottom of this page. If you have any questions please email help@researchandmarkets.com Order information Please verify that the product information is correct and select the format you require. 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