骨転移市場の動向

Abstract

Overview

Introduction

Bone metastases are a complication of some advanced cancers including cancers of the breast, lung, prostate, kidney and thyroid. The incidence of bone metastases across these tumor types in the seven major markets is forecasted to total 225,174 in 2008. While treatment with bisphosphonates reduces the risk of skeletal complications, they do not improve survival in the majority of patients.

Scope

• Overview of bone metastases epidemiology, which is currently unknown, disease mechanisms, complications and diagnosis
• Current treatment options and identification of unmet needs in bone metastases
• Research and analysis of the bone metastases pipeline with clinical and commercial assessment of late-phase candidates
• Stakeholder opinions based on qualitative interviews with key opinion leaders from the US and EU

Highlights

Current bisphosphonate therapy reduces the risk of skeletal complications such as fractures and bone pain but as yet do not offer a survival advantage in the majority of patients. More efficacious agents that improve survival and enhance the quality of life of advanced cancer patients with bone metastases would be highly welcome.

Survival of bone metastases patients varies according to primary cancer type and largely remains unchanged with current treatment. In light of this, an emerging opportunity is the potential of bisphosphonate therapy to prevent bone metastases when given in early stage cancer patients, for which trials are ongoing.

Approaching patent expiries for Bondronat and Zometa and the subsequent availability of cheaper generic versions may raise the barrier to uptake of more novel but costly emerging agents such as denosumab. However, significant opportunity exists to succeed in the bone metastases market if newer agents can demonstrate superior efficacy and/or safety.

Reasons to Purchase

• Gain an insight into the epidemiology trends as the true incidence of bone metastases is currently unknown
• Identify the limitations of current bone metastases therapy and consider the remaining unmet needs
• Acquire a detailed appreciation and impartial perspective of the bone metastases pipeline and identify the key products in late-phase development

Table of Contents

• ABOUT DATAMONITOR HEALTHCARE
  • About the Oncology pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of analysis
  • Datamonitor insight into bone metastases
  • Related reports
  • Upcoming reports
• CHAPTER 2 OVERVIEW OF BONE METASTASES
  • Bone metastases are a frequent complication of advanced cancers
  • Cancer cells commonly metastasize to the bone
    • The principles of cancer metastases
    • The ' seed and soil' hypothesis
  • Is bone a fertile ' soil' for metastatic growth?
    • The bone remodeling process
      • Bone resorption by osteoclasts
      • Bone formation by osteoblasts
  • Bone metastases cause dysregulation of the normal bone remodeling process
    • Osteolytic metastases
      • Cancer cells induce the formation of growth factors and cytokines involved in osteoclast activation
      • Parathyroid hormone-related peptide mediates osteolysis
      • The vicious cycle of osteolytic metastasis
    • Osteoblastic metastases
      • Endothelin-1 may be an important regulator of bone formation
      • Possible mediators of osteoblastic metastases
    • Anatomy and complications of bone metastases
      • Bone pain
      • Hypercalcemia
      • Pathological fractures
      • Spinal cord compression
    • Diagnosis of bone metastases
    • The value of biochemical markers of bone metabolism
  • Epidemiology
    • Incidence of advanced cancers
    • Estimated incidence of bone metastases
    • Multiple myeloma incidence
    • Survival of patients with bone metastases
• CHAPTER 3 CURRENT TREATMENT OPTIONS FOR BONE METASTASES
  • Introduction to bone metastases treatment
  • Bisphosphonates
    • Bisphosphonates reduce the risk of skeletal-related events
    • Pamidronate
      • Clinical trial data
    • Bondronat (ibandronate)
      • Clinical trial data
      • Ongoing clinical development
    • Clodronate
      • Clinical trial data
      • Ongoing clinical development of clodronate
    • Zometa (zoledronate)
      • Clinical trial data
      • Ongoing clinical development
    • The choice and duration of bisphosphonate therapy
      • The choice of administration is matched to patient needs
      • Zometa has significant advantages over other bisphosphonates
      • The duration of bisphosphonate therapy is based on clinical judgment
    • Adverse effects of bisphosphonates
      • Osteonecrosis of the jaw
    • Future directions for bisphosphonate therapy
      • Bisphosphonates reduce elevated levels of bone markers
      • Can bisphosphonates prevent bone metastases?
      • Reducing tumor burden by inhibiting bone metastases
  • Radiotherapy helps reduce bone pain
  • Radiopharmaceuticals
  • Surgery is often wrongly deemed "too risky"
• CHAPTER 4 UNMET NEEDS IN BONE METASTASES
  • There is a need to predict which patients will develop bone metastases
  • Patients may be on bisphosphonates for too long
  • New therapies required to improve current poor patient survival
  • Drugs needed to specifically target osteoblastic metastases
  • Summary of unmet needs
• CHAPTER 5 PIPELINE ANALYSIS
  • The bone metastases pipeline overview
  • Phase III drug profile
    • Denosumab (Amgen/Daiichi Sankyo)
      • Key historical events
      • Clinical trial data for denosumab
      • Clinical development of denosumab
      • Datamonitor comments
  • Phase II drug profiles
    • Alpharadin (AT1-BC-1; Algeta)
      • Key historical events
      • Clinical trial data for Alpharadin
      • Clinical development of Alpharadin
      • Datamonitor comments
    • MER-101 (Merrion)
      • Clinical development of MER-101
      • Datamonitor comments
    • Odanacatib (Merck)
      • Key Historical events
      • Clinical development of odanacatib
      • Datamonitor comments
• CHAPTER 6 KEY OPINION LEADERS INTERVIEWED
  • Key opinion leaders interviewed
• APPENDIX
  • Bibliography
    • Journals
    • Websites
    • Other
  • Abbreviations
  • List of tables
  • List of figures
  • About Datamonitor
    • About Datamonitor Healthcare
    • About the Oncology analysis team
  • Disclaimer
  • List of Tables
    • Table 1: Regulation of bone resorption
    • Table 2: Regulation of bone formation
    • Table 3: Biochemical markers of bone metabolism
    • Table 4: Total incidence of five cancer types across the seven major pharmaceutical markets, 2002-18
    • Table 5: Incidence of advanced cancers in the seven major pharmaceutical markets, 2002-18
    • Table 6: Incidence of advanced cancers in the seven major pharmaceutical markets in 2008
    • Table 7: Estimated incidence of bone metastases in five cancer types across the seven major pharmaceutical markets, 2002-18
    • Table 8: Estimated incidence of bone metastases in five cancer types across the seven major pharmaceutical markets in 2008
    • Table 9: Incidence of multiple myeloma in the seven major pharmaceutical markets, 2002-18
    • Table 10: Bisphosphonates approved for bone metastases in oncology, 2008
    • Table 11: Approval information for Bondronat in Oncology
    • Table 12: Ongoing Phase III development of Bondronat, 2008
    • Table 13: Ongoing Phase III development of clodronate
    • Table 14: Zometa reduces the risk of skeletal-related events across different tumor types
    • Table 15: Ongoing Phase III clinical development for Zometa, 2008
    • Table 16: Bisphosphonates: IV/oral regimens and potencies relative to Didronel*
    • Table 17: Study outcomes for Zometa in the prevention of bone metastases
    • Table 18: Phase III trial for the combination of radiopharmaceuticals with Zometa
    • Table 19: Pipeline drugs for bone metastases, 2008
    • Table 20: Denosumab: key historical events
    • Table 21: Denosumab: ongoing clinical trials in bone metastases
    • Table 22: Alpharadin: key historical events
    • Table 23: Alpharadin: ongoing clinical development in bone metastases
    • Table 24: Odanacatib: key historical events
    • Table 25: Odanacatib: ongoing clinical development in bone metastases
    • Table 26: Abbreviations used in Stakeholder Opinions: Bone Metastases, 2008
  • List of Figures
    • Figure 1: The principles of cancer metastases
    • Figure 2: Common sites of metastases for different primary cancers
    • Figure 3: The bone remodeling process
    • Figure 4: Osteoclast activation via RANKL/RANK binding on osteoclast precursors
    • Figure 5: The effect of osteoprotegerin on osteoclast activation
    • Figure 6: The vicious cycle of osteolytic metastasis
    • Figure 7: Factors involved in osteoblastic bone metastases
    • Figure 8: Skeletal regions most affected by bone metastases
    • Figure 9: Detecting bone metastases
    • Figure 10: Percentage incidence of bone metastases by advanced primary cancer type
    • Figure 11: Percentage incidence of advanced cancers
    • Figure 12: Generating the incidence of bone metastases*
    • Figure 13: Median and 5-year survival rates for bone metastases patients
    • Figure 14: A brief overview of bone metastases treatment
    • Figure 15: Pamidronate: results from two Phase III trials in breast cancer patients with bone metastases
    • Figure 16: Bondronat: Phase III trial results in breast cancer bone metastases patients
    • Figure 17: Clodronate trial results in breast cancer bone metastases patients
    • Figure 18: Zometa: Phase III results in breast and multiple myeloma patients
    • Figure 19: Adverse effects associated with bisphosphonate therapy
    • Figure 20: Unmet needs in bone metastases
    • Figure 21: Denosumab: mechanism of action
    • Figure 22: Denosumab: Phase II results in bisphosphonate-na・ e breast cancer patients
    • Figure 23: Alpharadin: Phase II results in hormone-refractory prostate cancer patients with bone metastases