Pipeline Insight: Osteoporosis - Intermittent dosing drives market growth

Table of Contents

• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of the analysis
  • Key metrics
  • Datamonitor Pipeline Assessment Summary
• CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS
  • Pipeline overview
    • Traditional, well-stocked pipeline
    • Growing PTH class hints at upcoming innovation
      • Reformulation as a substitute for innovation
    • Osteoporosis drug development not limited to big pharma
  • Key companies involved in the osteoporosis pipeline
    • Merck & Co.: coping with change
      • Merck' s line expands, but the patent is wide open
      • Limited hope in the pipeline
    • Novartis: an old player with new strategies
      • Osteoporosis indication a key driver in Zometa growth
      • New classes and patent expiration represent threats
    • GlaxoSmithKline: A newcomer with a long-term approach
      • Boniva as a learning curve
      • Pipeline hints at future success
  • Key R&D company strategies
    • Optimizing administration
      • Yearly dosing has potential as the next stage in intermittent dosing
      • Options in delivery mode maintain whole brand sales
    • The addition of mineral supplements: calcium and vitamin D
      • Additional dose calcium satisfies physicians' demands
      • Combining vitamin D aids Merck' s key brand' s lifecycle
    • Genericization: if you can not beat them, join them
• CHAPTER 3 OSTEOPOROSIS - MARKET POTENTIAL
  • Definition of osteoporosis
    • Etiology of osteoporosis
      • Osteoporosis classification: primary and secondary
      • Pathology and complications
      • Development of osteoporosis drugs
  • Segmentation of osteoporosis
  • Severity
    • Gender: osteoporosis in men
    • Niche populations
      • Glucocorticoid-induced osteoporosis
      • Paget' s disease
      • CNS disorder-related fracture risk
      • Ethnic diversity
      • Prostate cancer
      • Premature menopause
      • HIV
      • Anorexia nervosa
  • Epidemiology of osteoporosis
    • Methodological difficulties in assessing prevalence
    • Prevalence of osteoporosis and osteopenia in postmenopausal women
      • Overview of the prevalence of osteoporosis and osteopenia in postmenopausal women
      • US
      • Japan
      • France
      • Germany
      • Italy
      • Spain
      • UK
    • Prevalence of osteoporosis and osteopenia in men
      • Introduction
      • Overview of the prevalence of osteoporosis/osteopenia in men
      • US
      • Japan
      • France
      • Germany
      • Italy
      • Spain
      • UK
    • Osteoporotic fractures, their implications and minor risk groups
      • Introduction
      • Limitations of fracture prevalence data
      • Overview of fracture prevalence
      • US
      • Japan
      • France
      • Germany
      • Italy
      • Spain
      • UK
    • Epidemiological trends
  • Unmet needs in osteoporosis
    • Unmet clinical needs
      • Need for improved compliance
      • Need for efficacy at least equivalent to Fosamax and Actonel
      • Need for surrogate endpoint efficacy
      • Need for efficacy at the hip
    • Unmet environmental needs
      • Need for increased patient identification, treatment rates and use of appropriate treatments in each patient
      • Need for primary prevention in osteoporosis - preventing the first fracture reduces the future fracture burden
      • Need for greater recognition of secondary causes of osteoporosis
      • Need for greater recognition of male osteoporosis and causes of secondary osteoporosis in men for screening or case-finding purposes
• CHAPTER 4 R&D APPROACH
  • Classification of pipeline products
    • Bisphosphonates
      • Mechanism of action
      • Class breakdown
      • The gold standard therapy: Fosamax
      • Bisphosphonates threatened by genericization
      • Pipeline bisphosphonates
    • SERMs
      • Mechanism of action
      • Pipeline SERMs
    • Calcitonins
      • Mechanism of action
      • Pipeline calcitonins
    • Parathyroid hormone (PTH) and analogues
      • Mechanism of action
      • Pipeline PTH
    • Dual action bone agents (strontium ranelate)
      • Mechanism of action
      • Pipeline DABAs
    • Hormone replacement therapy (HRT)
      • Mechanism of action
      • Class breakdown
      • Pipeline hormonal therapies
    • Vitamin D
      • Mechanism of action
      • Pipeline vitamin D
    • Other mechanisms of action
      • Monoclonal antibodies
      • Cathepsin K inhibitors
  • Clinical trial design in osteoporosis
    • Clinical trial guidelines
      • Pre-clinical planning: use of animal models
      • Prevention and treatment: the implications for endpoint selection
      • Trial design and study population
    • Osteoporosis trial design and execution: can anything replace fracture data?
      • Problems with definitions: a need for greater consistency
      • Large-scale trials: can surrogate endpoints ever predict fracture risk?
      • The ethics of placebo-controlled trials: is there a realistic alternative?
      • Recruiting the right study population
  • Clinical trial endpoints in osteoporosis
    • Fracture rate
      • Significance of fracture rate as an endpoint
      • Considerations with fracture endpoints
    • Changes in BMD
      • Significance of BMD as an endpoint
      • Limitations of BMD as a clinical trial endpoint
    • Biochemical markers of bone turnover
      • How useful are bone markers?
      • Limitations in the use of bone-specific markers
    • Surrogate endpoints: predicting fracture risk
    • Changes in bone microarchitecture
      • Problems associated with microarchitecture assessment
• CHAPTER 5 BISPHOSPHONATE LATE-STAGE DRUG ANALYSIS AND FORECASTS
  • Comparative forecasts
  • Comparative Datamonitor drug assessment summaries
  • Overview for bisphosphonates
    • Definition of current comparator therapy - Fosamax
      • Clinical trial data
  • Aclasta/Reclast (zoledronate/zoledronic acid)
    • Drug profile
      • Clinical trial data
      • Patient potential
      • Marketing factors
    • Satisfaction of unmet needs
    • Forecasts to 2016
    • Datamonitor drug assessment summary
  • Bisponal/ONO-5920 (minodronic acid hydrate)
    • Drug profile
      • Clinical trial data
      • Patient potential
      • Market potential
    • Satisfaction of unmet needs
    • Forecasts to 2016
    • Datamonitor drug assessment summary
  • MER-103 (alendronate sodium)
    • Drug profile
      • Clinical trial data
      • Patient potential
      • Market potential
    • Satisfaction of unmet needs
    • Forecasts to 2016
    • Datamonitor drug assessment summary
  • Other drugs in the bisphosphonate class
    • Nerixia (neridronic acid)
      • Abiogen' s expertise may offset a halting development
• CHAPTER 6 SERMS LATE-STAGE DRUG ANALYSIS AND FORECASTS
  • Overview for SERMs
    • Definition of current comparator therapy - Evista
  • Bazedoxifene
    • Drug profile
      • Clinical trial data for the treatment of osteoporosis
      • Clinical trial data for the prevention of osteoporosis
      • Patient potential
      • Marketing factors
    • Satisfaction of unmet needs
    • Forecasts to 2016
  • Other drugs in the SERM class
    • Arzoxifene (LY353381)
      • Lilly' s Evista follow on?
    • PSK-3471
• CHAPTER 7 CALCITONIN LATE-STAGE DRUG ANALYSIS AND FORECASTS
  • Overview for calcitonins
    • Definition of current comparator therapy - Miacalcin
      • Clinical trial data
  • BN-002
    • Drug profile
      • Clinical trial data
      • Patient potential
      • Marketing factors
    • Satisfaction of unmet needs
    • Forecasts to 2016
• CHAPTER 8 PTH LATE-STAGE DRUG ANALYSIS AND FORECASTS
  • Comparative forecasts
  • Comparative Datamonitor drug assessment summaries
  • Overview of PTH
    • Definition of current comparator therapy - Forteo
  • hPTH (1-34)
    • Drug profile
      • Clinical trial data
      • Patient potential
      • Marketing factors
    • Satisfaction of unmet needs
    • Forecasts to 2016
  • Ostabolin-C
    • Drug profile
      • Clinical trials
      • Patient potential
      • Marketing potential
    • Satisfaction of unmet need
    • Forecasts to 2016
  • Other drugs in the PTH class
    • MBRI-93.02 (hPTH)
      • Unhampered development will allay looming class competition
• CHAPTER 9 OTHER DRUGS LATE-STAGE ANALYSIS AND FORECASTS
  • Comparative forecasts
  • Comparative Datamonitor drug assessment summaries
  • Overview of ' other drugs'
    • Definition of current comparator therapy
  • Denosumab (AMG-162)
    • Drug profile
      • Clinical trial data
      • Patient potential
      • Marketing potential
    • Satisfaction of unmet needs
    • Forecasts to 2016
  • ED-71
    • Drug profile
      • Clinical trial data
      • Patient potential
      • Marketing potential
    • Satisfaction of unmet needs
    • Forecasts to 2016
  • Other drugs in the class
    • MK-0822
      • Merck diversifies to cathepsin K inhibitors in the event of falling bisphosphonate sales
    • NBS-101
      • Clinical and commercial doubt surrounds DABA
    • SHT-546
• CHAPTER 10 INNOVATIVE EARLY-STAGE PROJECTS
  • Key Phase I compounds in osteoporosis
  • ACE-011
    • Potential to pioneer the provision of anti-resorptive and anabolic activity
      • Changing the face of osteoporosis treatment
      • Acceleron should optimize interest in ACE-011
  • 2MD
    • A high risk strategy for Pfizer
      • Early results indicate a potent anabolic agent
      • ED-71' s progress represents a useful guide
  • Raloxifene (extended release)
    • A reformulation to rival Evista
      • Proprietary technology improves bioavailability
      • External influences on SERM commercialization must be considered
• BIBLIOGRAPHY
  • Journal papers and conference abstracts
  • Websites
• APPENDIX A
  • Methodology
    • Market sizing
    • Estimated 2006 sales revenue
    • Osteoporosis specific sales calculations
    • Product forecasts
    • Estimation of launch dates
    • Definition of a standard unit
    • Japanese market data
    • Patient expiry and generic assumptions
  • Contributing experts
  • Report methodology
• APPENDIX B
  • About the Women' s Health analysis team
  • Disclaimer
  • List of Tables
    • Table 1: Forecast key pipeline products for osteoporosis in the seven major markets ($), 2006-2016
    • Table 2: R&D pipeline in osteoporosis, 2007
    • Table 3: Causes of secondary (Type III) osteoporosis
    • Table 4: World Health Organization classification of osteoporotic bone loss
    • Table 5: Epidemiology overview of osteoporosis
    • Table 6: Prevalence of osteopenia and osteoporosis in postmenopausal women across the seven major markets, 2007
    • Table 7: Prevalence of osteopenia and osteoporosis in men over 50 in the seven major markets, 2007
    • Table 8: Prevalence of vertebral fractures in men and women over 50 in the seven major markets, 2007
    • Table 9: UN projected population aged 50 years and over in 2017
    • Table 10: Summary of therapeutic classes in osteoporosis, by ATC code in alphabetical order
    • Table 11: Overview of currently marketed bisphosphonates indicated for use in osteoporosis treatment and prevention, 2007
    • Table 12: Overview of currently marketed SERM indicated for use in osteoporosis treatment and prevention, 2007
    • Table 13: Overview of currently marketed calcitonins indicated for use in osteoporosis treatment and prevention, 2007
    • Table 14: Overview of currently marketed PTH drugs indicated for use in osteoporosis treatment and prevention, 2007
    • Table 15: Overview of currently marketed DABA products indicated for use in osteoporosis treatment and prevention, 2007
    • Table 16: Quantitative measures used for clinical efficacy endpoints in osteoporosis
    • Table 17: Summary of the biochemical markers of bone resorption and formation used to measure rate of bone turnover
    • Table 18: Late-stage bisphosphonates in development for osteoporosis
    • Table 19: Fosamax: key facts
    • Table 20: Defining the gold standard: key clinical trial results for Fosamax
    • Table 21: Novartis' s HORIZON trial design, 2003
    • Table 22: Key events, approval and launch dates impacting Aclasta revenue forecasts for osteoporosis in the seven major markets, 2007-2016
    • Table 23: Key events, approval and launch dates impacting Bisponal revenue forecasts for osteoporosis in the seven major markets, 2007-2016
    • Table 24: Key events, approval and launch dates impacting MER-103 revenue forecasts for osteoporosis in the seven major markets, 2007-2016
    • Table 25: Late-stage SERMs in development for osteoporosis
    • Table 26: Evista key facts
    • Table 27: Key events, approval and launch dates impacting bazedoxifene revenue forecasts for osteoporosis in the seven major markets, 2007-2016
    • Table 28: Late-stage calcitonins in development for osteoporosis
    • Table 29: Miacalcin: key facts
    • Table 30: Forthcoming trials for BN-002
    • Table 31: Key events, approval and launch dates impacting BN-002 revenue forecasts for osteoporosis in the seven major markets, 2007-2016
    • Table 32: Late-stage PTH in development for osteoporosis
    • Table 33: Forteo: key facts
    • Table 34: Key events, approval and launch dates impacting hPTH revenue forecasts for osteoporosis in the seven major markets, 2007-2016
    • Table 35: Key events, approval and launch dates impacting Ostabolin-C revenue forecasts for osteoporosis in the seven major markets, 2007-2016
    • Table 36: Other late-stage drugs in development for osteoporosis
    • Table 37: Key events, approval and launch dates impacting Denosumab revenue forecasts for osteoporosis in the seven major markets, 2007-2016
    • Table 38: Key events, approval and launch dates impacting ED-71 revenue forecasts for osteoporosis in the seven major markets, 2007-2016
    • Table 39: Drugs in Phase I and preclinical development for osteoporosis, 2007
    • Table 40: Summary of therapeutic classes in osteoporosis, by ATC code in alphabetical order
    • Table 41: Estimation of launch dates by phase of development
    • Table 42: Estimated generic discounts by country, 2006*
    • Table 43: Estimates of brand erosion by following patent expiry by country
    • Table 44: Weightings of research and clinical factors used for pipeline drug assessment
    • Table 45: Weightings of commercial factors used for pipeline drug assessment
  • List of Figures
    • Figure 1:osteoporosis drug assessment summary for the seven major markets, 2007-2016
    • Figure 2: Osteoporosis pipeline breakdown by development phase, 2007
    • Figure 3: The osteoporosis pipeline by phase and class of drug, 2007
    • Figure 4: Osteoporosis drugs and their overlap into other indications
    • Figure 5: Unmet clinical needs in osteoporosis, 2007
    • Figure 6: Unmet environmental needs in osteoporosis, 2007
    • Figure 7: Schematic showing steps of vitamin D activation