Pipeline Insight: Osteoporosis - The Science of Compliance

Table of Contents

• ABOUT DATAMONITOR HEALTHCARE
  • About the Womens Health pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of the analysis
  • Datamonitor insight into the disease osteoporosis market
  • Key metrics
  • Datamonitor Pipeline Assessment Summary
• CHAPTER 2 PIPELINE OVERVIEW AND FUTURE FOCUS
  • Key conclusions regarding top-line view of pipeline
    • A diverse pipeline ready to burst
      • PTH therapies and reformulations throughout the pipeline
  • Key companies involved in the osteoporosis pipeline
    • Pfizer - market entry setback as Oporia stumbles at FDA
      • What were the reasons for rejection and what arePfizers options?
      • Potential strategic options and impact on Oporiaslaunch date estimates and future revenues
    • Novartis
      • Missing the bone-formation boat?
      • Patent expiration could leave new indications at risk.Are dosing reformulations enough to protect them?
    • GlaxoSmithKline - A newcomer with a long-term approach
    • Chugai - a major player in Japan
    • Merck - managing the Fosamax lifecycle
      • Mercks line expands, but the patent is wide open
      • Missing long-term investment opportunities
• CHAPTER 3 PIPELINE DYNAMICS
  • Definition of osteoporosis
    • Etiology of osteoporosis
      • Osteoporosis classification: primary and secondary
      • Pathology and complications
      • Drug targets in osteoporosis
      • Development of osteoporosis drugs
  • Epidemiology of osteoporosis
    • Methodological difficulties in assessing prevalence
    • Prevalence of osteoporosis and osteopenia inpostmenopausal women
      • Overview of the prevalence of osteoporosis andosteopenia in postmenopausal women
      • US
      • Japan
      • France
      • Germany
      • Italy
      • Spain
      • UK
  • Segmentation of osteoporosis
    • Prevalence of osteoporosis and osteopenia in men
      • Introduction
      • Overview of the prevalence of osteoporosis/osteopenia inmen
      • US
      • Japan
      • France
      • Germany
      • Italy
      • Spain
      • UK
    • Osteoporotic fractures, their implications and minorrisk groups
      • Introduction
      • Limitations of fracture prevalence data
      • Overview of fracture prevalence
      • US
      • Japan
      • France
      • Germany
      • Italy
      • Spain
      • UK
    • Niche populations
      • Glucocorticoid-induced osteoporosis
      • Anorexia nervosa
      • HIV
      • CNS disorder-related bone loss
      • Pagets disease
      • Ethnic diversity
      • Premature menopause
  • Unmet needs in osteoporosis
    • Unmet clinical needs
      • Need for improved compliance
      • Need for efficacy at the hip - BMD and fractures
      • Need for efficacy at the spine - equivalent to Fosamaxand Actonel in fractures and BMD
      • Need for additional bone-forming agents - alternativeformulations, better safety profile, efficacy at the hip
      • Need for surrogate endpoint efficacy - suppression ofresorption and maintenance or up-regulation of formation
    • Unmet environmental needs
      • Need for greater recognition of secondary causes ofosteoporosis
      • Need for greater recognition of male osteoporosis andcauses of secondary osteoporosis in men for screening or case-findingpurposes
      • Need for primary prevention in osteoporosis - preventingthe first fracture reduces the future fracture burden
      • Need for increased patient identification, treatmentrates and use of appropriate treatments in each patient
• CHAPTER 4 R&D APPROACH
  • Classification of pipeline products
    • Bisphosphonates
      • Mechanism of action
      • Class breakdown
      • The gold standard therapy: Fosamax
    • SERMs
      • Mechanism of action
    • Calcitonins
      • Mechanism of action
    • Parathyroid hormone (PTH) and analogues
      • Mechanism of action
    • Hormone therapy
      • Mechanism of action
      • Class breakdown
    • Vitamin D
      • Mechanism of action
  • Clinical trial design in osteoporosis
    • Clinical trial guidelines
      • Pre-clinical planning: use of animal models
      • Prevention and treatment: the implications for endpointselection
      • Trial design and study population
    • Osteoporosis trial design and execution: can anythingreplace fracture data?
      • Problems with definitions: a need for greaterconsistency
      • Large-scale trials: can surrogate endpoints ever predictfracture risk?
      • The ethics of placebo-controlled trials: is there arealistic 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 BISPHOSPHONATES LATE-STAGE DRUG ANALYSIS &FORECASTS
  • Overview for the bisphosphonates
    • Pipeline summary
  • Definition of current comparator therapy - Fosamax
    • Clinical trial data
  • Fosamax Plus D (alendronate and cholecalciferol)
    • Drug overview
      • Pipeline attractiveness
      • Forecast
  • Boniva (ibandronate)
    • Drug overview
      • Clinical trial data
      • Patient potential
      • Marketing factors
    • Satisfaction of unmet needs
    • Pipeline attractiveness
    • Forecasts
  • Aclasta (zoledronate)
    • Drug overview
      • Clinical trial data
      • Patient potential
      • Marketing factors
    • Satisfaction of unmet needs
    • Pipeline attractiveness
    • Forecasts
  • Comparison of key compounds in the bisphosphonate class
• CHAPTER 6 SERMS LATE-STAGE DRUG ANALYSIS AND FORECASTS
  • Overview for the SERMs
    • Pipeline summary
  • Definition of current comparator therapy - Evista
  • Comparative analysis
  • Oporia (lasofoxifene)
    • Drug overview
      • Clinical trial data
      • Ongoing late-stage clinical trials
      • Patient potential
      • Marketing factors, ambitious plans for simultaneousglobal launch
    • Satisfaction of unmet needs
    • Pipeline attractiveness
    • Forecasts
  • Bazedoxifene
    • Drug overview
      • Clinical trial data
      • Bazedoxifene and Premarin
      • Patient potential
      • Marketing factors, overcoming negative hormone therapyperceptions
    • Satisfaction of unmet needs
    • Pipeline attractiveness
    • Forecasts
  • Comparison of key compounds in the SERM class
• CHAPTER 7 PTH LATE-STAGE DRUG ANALYSIS
  • Overview for PTH class
    • Pipeline summary
  • Definition of current comparator therapy - Forteo
  • Comparative analysis
  • Preos/Preotact (rhPTH 1-84)
    • Drug overview
      • Clinical trial data
      • Patient potential
      • Marketing factors
    • Satisfaction of unmet needs
    • Pipeline attractiveness
    • Forecasts to 2015
  • Other PTH drugs in development
    • Asahi Kasei Pharma - teriparatide/PTH (1-34)
  • Comparison of key compounds in the PTH class
• CHAPTER 8 CALCITONIN LATE-STAGE DRUG ANALYSIS
  • Overview of the calcitonins
    • Pipeline overview
  • Definition of current comparator therapy - Miacalcin
    • Clinical trial data
  • Comparative analysis
  • Fortical
    • Drug overview
      • Clinical trial data
      • Patient and marketing potential
    • Satisfaction of unmet needs
    • Pipeline attractiveness
    • Forecasts
• CHAPTER 9 OTHER DRUGS LATE-STAGE DRUG ANALYSIS
  • Pipeline Overview
    • Definition of current comparator therapy
  • Comparative analysis
    • Protelos (strontium ranelate)
      • Drug overview
      • Clinical trial data
      • Patient potential
      • Marketing factors
    • Satisfaction of clinical unmet needs
    • Pipeline attractiveness
    • Forecasts
  • Denusomab (AMG-162)
    • Drug overview
      • Clinical trial data
      • Patient and marketing potential
    • Satisfaction of unmet needs
    • Pipeline attractiveness
    • Forecasts
  • ED-71
    • Drug Overview
      • Clinical trial data
      • Patient and marketing potential
    • Satisfaction of unmet needs
    • Pipeline attractiveness
    • Forecasts
  • Comparison of key compounds in the Others class
• CHAPTER 10 INNOVATIVE EARLY-STAGE PROJECTS
  • Key Preclinical compounds in osteoporosis
  • Src kinase inhibitors
  • Vitronectin receptor antagonists
    • GSK - SB 273005
  • Long-acting proteins
    • Human Genome Sciences
• APPENDIX A
  • Methodology
    • Datamonitor forecast methodology
    • Datamonitor drug assessment summary
  • Bibliography
    • Epidemiology
      • United States
      • Japan
      • France
      • Germany
      • Italy
      • Spain
      • UK
      • General
    • Clinical trial data
  • Report methodology
• APPENDIX B
  • About Datamonitor
    • About Datamonitor Healthcare
  • Datamonitor Healthcares therapy area capabilities
    • About the cardiovascular analysis team
  • Disclaimer
• List of Tables
  • Table 1: Global forecast for top five pipeline drugsand total osteoporosis market ($m), 2005-15
  • Table 2: Summary of commercial and research/clinicalattractiveness of top five late-phase drugs for osteoporosis
  • Table 3: R&D pipeline in osteoporosis, 2005
  • Table 4: Number of key osteoporosis drugs by class anddevelopment phase, 2005
  • Table 5: Summary of PTH therapies in development forosteoporosis
  • Table 6: Causes of secondary (Type III) osteoporosis
  • Table 7: World Health Organization classification ofosteoporotic bone loss
  • Table 8: Epidemiology overview of osteoporosis
  • Table 9: Prevalence of osteopenia and osteoporosis inpostmenopausal women across the seven major markets, 2005
  • Table 10: Prevalence of osteopenia and osteoporosis inmen over 50 in the seven major markets, 2005
  • Table 11: Prevalence of vertebral fractures in men andwomen over 50 in the seven major markets, 2005
  • Table 12: Summary of therapeutic classes inosteoporosis, by ATC code in alphabetical order
  • Table 13: Regional patent expiration ofcurrently-marketed osteoporosis drugs
  • Table 14: Overview of currently-marketedbisphosphonates indicated for use in osteoporosis treatment andprevention
  • Table 15: Overview of currently-marketed SERMsindicated for use in osteoporosis treatment and prevention
  • Table 16: Overview of currently-marketed calcitoninsindicated for use in osteoporosis treatment
  • Table 17: Overview of currently marketed PTH drugsindicated for use in osteoporosis treatment
  • Table 18: Quantitative measures used for clinicalefficacy endpoints in osteoporosis
  • Table 19: Summary of the biochemical markers of boneresorption and formation used to measure rate of bone turnover
  • Table 20: Summary of bisphosphonate products inlate-stage development for osteoporosis
  • Table 21: Fosamax: Key facts
  • Table 22: Defining the gold standard: key clinicaltrial results for Fosamax
  • Table 23: Summary of products within the Fosamax brand
  • Table 24: Dose ranging study results for 20mg andplacebo with ibandronate, % change from baseline
  • Table 25: Summary of Phase II trials of ibandronate inpostmenopausal osteoporosis
  • Table 26: Results at 2 and 3 years in study comparing3-monthly i.v. ibandronate, and daily oral alfacalcidol, % BMD relativeto baseline, 2003
  • Table 27: Factors affecting forecast revenues ofBoniva (oral and IV), 2005-15
  • Table 28: Novartiss HORIZON trial design, 2003
  • Table 29: Factors affecting forecast revenues ofAclasta, 2008-15
  • Table 30: Global sales forecasts for bisphosphonates,2005-15
  • Table 31: SERMs late-stage pipeline summary
  • Table 32: Evista: key facts
  • Table 33: Percentage change in bone turnover markerswith lasofoxifene after six months
  • Table 34: Mean percentage change from baseline at 24months
  • Table 35: Factors affecting forecast revenues ofOporia, 2008-15
  • Table 36: Factors affecting forecast revenues ofbazedoxifene and bazedoxifene/Premarin, 2008-15
  • Table 37: Global sales forecasts for SERMs, 2007-15
  • Table 38: Summary of PTH drugs in late-stagedevelopment for osteoporosis
  • Table 39: Forteo: key facts
  • Table 40: Results of PATH trial (%), 2003
  • Table 41: Factors affecting forecast revenues ofPreos/Preotact, 2008-15
  • Table 42: Overview of the calcitonins in late-stagedevelopment for the prevention or treatment of osteoporosis
  • Table 43: Miacalcin: key facts
  • Table 44: Factors affecting forecast revenues ofFortical, 2008-15
  • Table 45: Overview of Other drugs in late-stagedevelopment for the prevention and treatment of osteoporosis, 2005
  • Table 46: Study population, design and endpoints.
  • Table 47: PREVOS change in BMD results, percent frombaseline
  • Table 48: STRATOS mean annual change in BMD, percentfrom baseline
  • Table 49: Factors affecting forecast revenues ofProtelos, 2008-15
  • Table 50: Factors affecting forecast revenues ofED-71, 2008-15
  • Table 51: Global sales forecasts for Other drugs,2005-15
  • Table 52: Drugs in development for osteoporosis, 2005
• List of Figures
  • Figure 1: Datamonitor osteoporosis drug assessmentsummary
  • Figure 2: Osteoporosis pipeline breakdown bydevelopment phase shows heavily pregnant late-stage pipeline
  • Figure 3: Pipeline overview of osteoporosis drugs
  • Figure 4: Pfizers possible actions in response to FDA"not approvable" letter on Oporia for osteoporosis prevention
  • Figure 5: US Oporia forecast comparing Datamonitorspotential sales estimates before and after FDA gave its not approvableverdict
  • Figure 6: Forecast of Fosamax brand, generic and totalmolecule sales in the US, 2004-15
  • Figure 7: Schematic of key current and pipeline drugs,their targets and their effects on bone formation and resorption
  • Figure 8: Osteoporosis drugs and their overlap intoother indications
  • Figure 9: Prevalence of osteopenia and osteoporosis inwomen over 50 years across the seven major markets, 2005
  • Figure 10: Prevalence of osteopenia and osteoporosisin men over 50 in the seven major markets, 2005
  • Figure 11: Prevalence of vertebral fractures in menand women over 50 across the seven major markets, 2005
  • Figure 12: Unmet clinical needs in osteoporosis
  • Figure 13: Schematic showing steps of vitamin Dactivation
  • Figure 14: Pipeline attractiveness of Fosamax PlusD/Fosavance in osteoporosis
  • Figure 15: Osteoporosis sales forecast for FosamaxPlus D in osteoporosis to 2015
  • Figure 16: SWOT analysis of Boniva for osteoporosis
  • Figure 17: Assessment of Boniva key performanceindicators
  • Figure 18: Pipeline attractiveness of Boniva inosteoporosis
  • Figure 19: Global sales forecast for Boniva (oral andIV) in osteoporosis to 2015
  • Figure 20: SWOT analysis of Aclasta for osteoporosis
  • Figure 21: Assessment of Aclasta key performanceindicators
  • Figure 22: Pipeline attractiveness of Aclasta inosteoporosis
  • Figure 23: Global sales forecast for Aclasta inosteoporosis to 2015
  • Figure 24: Datamonitors drug assessment summary forthe late-stage pipeline bisphosphonate therapies
  • Figure 25: Global sales forecasts for bisphosphonates,2005-15
  • Figure 26: SWOT analysis of Oporia in osteoporosis
  • Figure 27: Assessment of Oporia key performanceindicators
  • Figure 28: Pipeline attractiveness of Oporia forosteoporosis
  • Figure 29: Global sales forecast for Oporia inosteoporosis to 2015
  • Figure 30: SWOT analysis of bazedoxifene inosteoporosis
  • Figure 31: Assessment of bazedoxifene key performanceindicators
  • Figure 32: Pipeline attractiveness of bazedoxifene andbazedoxifene plus Premarin for osteoporosis
  • Figure 33: Global sales forecast for bazedoxifene andbazedoxifene/Premarin in osteoporosis to 2015
  • Figure 34: Datamonitors drug assessment summary forthe late-stage pipeline SERM therapies
  • Figure 35: Global sales forecasts for SERMs, 2007-15
  • Figure 36: SWOT analysis of Preos in osteoporosis
  • Figure 37: Assessment of Preos key performanceindicators
  • Figure 38: Pipeline attractiveness of Preos forosteoporosis
  • Figure 39: Global sales forecast for Preos/Preotact inosteoporosis to 2015
  • Figure 40: Datamonitors drug assessment summary forthe late-stage pipeline PTH therapies
  • Figure 41: SWOT analysis of Fortical in osteoporosis
  • Figure 42: Assessment of Fortical key performanceindicators
  • Figure 43: Pipeline attractiveness of Fortical forosteoporosis
  • Figure 44: Global sales forecast for Fortical inosteoporosis to 2015
  • Figure 45: SWOT analysis of Protelos in osteoporosis
  • Figure 46: Assessment of Protelos key performanceindicators
  • Figure 47: Pipeline attractiveness of Protelos forosteoporosis
  • Figure 48: Global sales forecast for Protelos inosteoporosis to 2015
  • Figure 49: SWOT analysis of Denosumab in osteoporosis
  • Figure 50: Assessment of Denosumab key performanceindicators
  • Figure 51: Pipeline attractiveness of Denosumab inosteoporosis
  • Figure 52: Global sales forecast for Denosumab inosteoporosis to 2015
  • Figure 53: SWOT analysis of ED-71 in osteoporosis
  • Figure 54: Assessment of ED-71 key performanceindicators
  • Figure 55: Pipeline attractiveness of ED-71 forosteoporosis
  • Figure 56: Global sales forecast for ED-71 inosteoporosis to 2015
  • Figure 57: Datamonitors drug assessment summary forthe late-stage pipeline Other therapies
  • Figure 58: Global sales forecasts for Other drugs,2005-15