Abstract
Overview
Introduction
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic
stem cell disorders. With a forecast incidence of 36,769 across the seven
major markets in 2007, they are one of the most common hematological
malignancies. Currently, the only potentially curative option is hematopoietic
stem cell transplantation but this is only suitable for a small subset of
patients.
Scope
- MDS epidemiology, disease diagnosis and overview of current treatment
options
- Remaining unmet needs in the treatment of MDS
- Research and analysis of the MDS pipeline with in-depth clinical
assessment of Phase III candidates
- Stakeholder opinions based on qualitative interviews with key opinion
leaders from the US and EU
Report Highlights
Patients' old age and associated co-morbidities often prohibit the use of
high-intensity therapies such as hematopoietic stem cell transplantation.
Therefore, most patients rely on supportive care and low-intensity therapies
for the management of the disease.
While low-intensity therapies such as Vidaza, Dacogen and Revlimid have
improved patient outcomes, higher-risk MDS remains a disease with poor
prognosis. Therefore, there is a great need for more effective drugs with
favorable toxicity profiles to improve patient survival and quality of life.
Recent approvals have spurred interest in MDS but this has yet to be
translated into considerable R&D efforts in the field. There is only one drug
in Phase III development, Schering-Plough' s Sarasar (lonafarnib). This
molecular targeted therapy is unlikely to offer any significant improvements
over existing therapies.
Reasons to Purchase
- Gain an insight into the current classification systems and the
epidemiology trends for MDS
- Identify the limitations of current MDS treatment options and consider the
remaining unmet needs
- Acquire a detailed appreciation and impartial perspective of the MDS
pipeline
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
- 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
- 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
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