Stakeholder Opinions: Myelodysplastic Syndromes - First approvals spur some interest in a niche market

Table of Contents

• ABOUT DATAMONITOR HEALTHCARE
  • About the Oncology pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of analysis
  • Datamonitor insight into the MDS market
  • Related reports
  • Upcoming reports
• CHAPTER 2 OVERVIEW OF MYELODYSPLASTIC SYNDROMES
  • Introduction
    • Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies
    • Risk factors in the development of MDS
    • Hallmark of MDS - A hypercellular bone marrow with dysplastic changes in combination with peripheral cytopenias
      • Hypercellularity
      • Dysplasia
      • Peripheral cytopenias
    • Mortality often results from the complications of peripheral blood cytopenias
    • MDS is often a diagnosis of exclusion
    • The molecular pathogenesis of MDS
      • Chromosomal abnormalities are common but little is known about the molecular basis of the disease
      • MDS arises as a multistep process
      • Accelerated apoptosis underlies the cytopenias in early MDS
      • Excessive proliferation accompanies disease progression
  • The classification of MDS
    • French American British (FAB) System
      • The FAB classification system is based on morphological criteria
      • Limitations of the FAB system
    • World Health Organization (WHO) System
      • The WHO classification system incorporates new diagnostic information
      • Classification of chronic myelomonocytic leukemia (CMML)
      • Limitations of the WHO classification system
    • International Prognostic Scoring System (IPSS)
      • The IPSS classification system is the current standard for evaluating prognosis in MDS patients
      • Limitations of the IPSS system
  • Epidemiology
    • The epidemiology of MDS is poorly monitored
    • MDS is predominantly a disease of the elderly
    • A recent study shows that the majority of patients fall into the IPSS Low and Intermediate-1 risk groups
    • The incidence of MDS is expected to rise
    • There will be more than 57,000 new cases of MDS across the seven major markets in 2016
• CHAPTER 3 CURRENT TREATMENT OPTIONS FOR MDS
  • Overview of MDS management
    • The aim of treatment differs in lower- and higher-risk patients
    • The choice of therapy is not solely dependent on a patient' s IPSS risk group
  • Summary of current trends in MDS management
  • The management of IPSS lower-risk MDS patients
    • Supportive care approaches
      • Red blood cell (RBC) transfusion and iron chelation therapy
      • Erythropoietin (EPO)
      • Granulocyte-colony stimulating factor (G-CSF)
      • Platelet transfusions
    • Non-chemotherapy low-intensity agents
      • Thalomid (thalidomide; Celgene/Pharmion)
      • Revlimid (lenalidomide; Celgene)
      • Antithymocyte globulin and cyclosporin A
      • Anti-TNF therapy
      • Vitamin D analogs
    • Low-intensity chemotherapy
      • Vidaza and Dacogen
  • The management of IPSS higher-risk patients
    • Low-intensity chemotherapy - the hypomethylating agents
      • Vidaza (azacitidine; Pharmion)
      • Dacogen (decitabine; MGI Pharma)
      • Comparisons between Vidaza and Dacogen
    • Hematopoietic stem cell transplantation
      • HSCT is the only potentially curative option for MDS patients but its use in older patients is problematic
      • The morbidity and mortality risks associated with HSCT often prohibits its use in lower-risk patients
      • Different transplantation options exist for the treatment of MDS
    • High-intensity chemotherapy
      • High-intensity chemotherapy is an alternative option for higher-risk patients
      • The use of high-intensity chemotherapy may be difficult to justify
  • The management of CMML
    • Supportive care and low-intensity therapy
    • High-intensity therapy
• CHAPTER 4 UNMET NEEDS IN MDS
  • Summary of unmet needs
    • A better understanding of the molecular pathogenesis
    • Increased R&D efforts
    • Low-intensity therapies with improved efficacy and better toxicity profiles
    • Low-intensity therapies to improve symptoms of anemia and quality of life
    • More effective management of thrombocytopenia
    • Improved HSCT procedures
• CHAPTER 5 PIPELINE ANALYSIS
  • Summary
  • Pipeline overview
    • Late-phase product pipeline for MDS
    • Phase II product pipeline for MDS
    • Phase I product pipeline for MDS
  • Late-phase MDS drug profiles
    • Sarasar (Lonafarnib; Schering-Plough)
      • Drug overview
      • Key historical events
      • Clinical trial data
      • Datamonitor comments
  • Phase II MDS drug profiles
    • MGCD0103 (Pharmion/MethylGene)
      • Drug overview
      • Key historical events
      • Clinical trial data
    • Romiplostim (Amgen)
      • Drug overview
      • Key historical events
      • Clinical trial data
    • Ceflatonin (Myelostat; ChemGenex Pharmaceuticals)
      • Drug overview
      • Key historical events
      • Clinical trial data
    • Zarnestra (Tipifarnib; Johnson & Johnson)
      • Drug overview
      • Key historical events
      • Clinical trial data
    • Cloretazine (VNP40101M; Vion Pharmaceuticals)
      • Drug overview
      • Key historical events
      • Clinical trial data
    • Clolar/Evoltra (Clofarabine; Genzyme)
      • Drug overview
      • Key historical events
      • Clinical trial data
    • Telintra (TLK-199; Telik)
      • Drug overview
      • Key historical events
      • Clinical trial data
• APPENDIX
  • Bibliography
    • Journals
    • Websites
    • Other
  • Key opinion leaders
  • List of tables
  • List of figures
  • Abbreviations
  • About Datamonitor
    • About Datamonitor Healthcare
    • About the Oncology analysis team
  • Disclaimer
  • List of Tables
    • Table 1: Myelodysplastic syndromes (MDS)
    • Table 2: Common recurring chromosomal abnormalities in MDS
    • Table 3: French American British (FAB) classification of MDS
    • Table 4: World Health Organization (WHO) classification of MDS
    • Table 5: WHO classification of myelodysplastic/myeloproliferative diseases (MDS/MPD)
    • Table 6: Survival and progression to AML for MDS patients within the IPSS risk groups
    • Table 7: IPSS classification of MDS patients
    • Table 8: MDS incidence in the seven major markets, 2002-2016
    • Table 9: Treatment guidelines for MDS
    • Table 10: Iron chelators available in the US and EU markets, 2007
    • Table 11: Branded erythropoietins available in the US and EU markets, 2007
    • Table 12: Erythropoietins: ongoing clinical trials in MDS, 2007
    • Table 13: Branded colony-stimulating factors available in the US and EU, 2007
    • Table 14: Thalomid: key historical events
    • Table 15: Thalomid as a single agent in MDS: clinical trial results
    • Table 16: Revlimid: key historical events
    • Table 17: Revlimid: ongoing clinical trials in MDS, 2007
    • Table 18: Antithymocyte globulin (ATG) available in the US and EU, 2007
    • Table 19: Antithymocyte globulin: ongoing clinical trials in MDS, 2007
    • Table 20: Vidaza: Key historical events
    • Table 21: Vidaza: ongoing clinical trials in MDS, 2007
    • Table 22: Response criteria used in the Phase III study of Vidaza versus supportive care in MDS patients
    • Table 23: Dacogen: key historical events
    • Table 24: Dacogen: ongoing clinical trials in MDS, 2007
    • Table 25: Response criteria used in the Phase III study of Dacogen versus supportive care in MDS patients
    • Table 26: Types of hematopoietic stem cell transplantation (HSCT)
    • Table 27: Comparative results of RIC HSCT studies
    • Table 28: High-intensity chemotherapy regimens in MDS: clinical trial results
    • Table 29: Pipeline drugs in Phase III development for MDS, 2007
    • Table 30: Pipeline drugs in Phase II development for MDS, 2007
    • Table 31: Pipeline drugs in Phase I development for MDS, 2007
    • Table 32: Sarasar: key historical events
    • Table 33: Ongoing clinical trials involving Sarasar in MDS, 2007
    • Table 34: MGCD0103: key historical events
    • Table 35: Ongoing clinical trials for MGCD0103 in MDS, 2007
    • Table 36: Romiplostim: key historical events
    • Table 37: Ongoing clinical trials for Romiplostim in MDS, 2007
    • Table 38: Ceflatonin: Key historical events
    • Table 39: Zarnestra: Key historical events
    • Table 40: Ongoing clinical trials involving Zarnestra in MDS, 2007
    • Table 41: Final results from a Phase II study of Zarnestra in Intermediate- and High-risk MDS
    • Table 42: Cloretazine: Key historical events
    • Table 43: Ongoing clinical trials involving Cloretazine in MDS, 2007
    • Table 44: Clolar: Key historical events
    • Table 45: Ongoing clinical trials involving Clolar in MDS, 2007
    • Table 46: Telintra: key historical events
    • Table 47: Ongoing clinical trials involving Telintra in MDS, 2007
    • Table 48: Abbreviations used in Stakeholder Opinions: Myelodysplastic Syndromes
  • List of Figures
    • Figure 1: Risk factors implicated in the onset of MDS
    • Figure 2: The hematopoiesis process
    • Figure 3: Hypercellularity and peripheral blood cytopenias in MDS
    • Figure 4: The pathophysiology of MDS
    • Figure 5: Median survival for each WHO MDS subtype
    • Figure 6: Cumulative risk of progressing to AML after 2 years for each MDS WHO subtype
    • Figure 7: International Prognostic Scoring System (IPSS) for MDS
    • Figure 8: Male and female incidence of MDS in the US over and under 65 years of age as a percentage of the total US patient population, 2007
    • Figure 9: MDS incidence in the seven major markets, 2007 and 2016
    • Figure 10: Incidence of MDS subtypes in the seven major markets, 2007
    • Figure 11: Factors complicating the management of MDS
    • Figure 12: Summary of supportive care, low-intensity and high-intensity therapies available for the management of MDS
    • Figure 13: Summary of current trends in the management of lower-risk MDS
    • Figure 14: Summary of current trends in the management of higher-risk MDS
    • Figure 15: NCCN treatment guidelines for lower-risk MDS patients (IPSS Low/Intermediate-1)
    • Figure 16: The implications of long-term transfusion dependence
    • Figure 17: Thrombocytopenia in MDS
    • Figure 18: Phase II study of Revlimid in MDS patients with del(5q)
    • Figure 19: Phase II study of Revlimid in MDS patients without del(5q)
    • Figure 20: Phase II study of Revlimid in Intermediate-2/High-risk MDS with del(5q): Interim results
    • Figure 21: Phase III study of Lymphoglobuline with cyclosporine versus best supportive care in Low/Intermediate-1 MDS
    • Figure 22: NCCN treatment guidelines for IPSS Intermediate-2/High-risk MDS patients
    • Figure 23: Phase III study of Vidaza versus supportive care in MDS patients
    • Figure 24: Phase III study of Vidaza versus conventional care regimens in higher-risk MDS
    • Figure 25: Phase III study of Dacogen versus supportive care in patients with MDS
    • Figure 26: US sales of Vidaza and Dacogen, Q1 2006-Q3 2007
    • Figure 27: Summary of unmet needs in the treatment of MDS
    • Figure 28: Clinical development pipeline for MDS, 2007
    • Figure 29: Proteins undergoing farnesylation by farnesyltransferase
    • Figure 30: Phase I/II study of Sarasar in advanced MDS and CMML
    • Figure 31: Phase I/II study of Romiplostim in Low-risk/Intermediate-1 MDS
    • Figure 32: Proteins undergoing farnesylation by farnesyltransferase
    • Figure 33: Phase II study of Zarnestra in Intermediate and High-risk MDS
    • Figure 34: Phase II study of Cloretazine in AML and high-risk MDS
    • Figure 35: Phase II studies of intravenous and oral Clolar in higher-risk MDS
    • Figure 36: Phase I/II study of intravenous Telintra (liposomes for injection) in MDS