Stakeholder Opinions: Bone Metastases - Impending patent expiries may help make or break newer agents

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