Pipeline Insight: Osteoporosis - Intermittent dosing drives market growth

SUMMARY

Introduction

The long-standing unmet need of the osteoporosis market has been for improved adherence to treatment. Two pipeline products, Amgen's Denosumab and Novartis' Aclasta (zoledronate), have answered this demand with intermittent dosing schedules and consequently are expected to generate blockbuster revenues. This will rejuvenate the market which is otherwise stalling under multiple patent expiries.

Scope

• Analysis of patient potential, unmet needs and clinical trial design in osteoporosis
• Overview of drugs in late- and early-stage clinical development; with analysis of key companies involved in the R&D pipeline
• Detailed profiles of key compounds in development for use in osteoporosis, with forecasts of drug revenues to 2016
• Review of the key strategies adopted by current market players

Report Highlights

Despite the genericization of the market leader Fosamax and patent expiries on other key brands, pipeline products are still viable. Datamonitor expects pipeline products to swell the total market value 4.4% between 2007 and 2016 to $10.9 billion.

Products that offer intermittent dosing schedules are highly desirable in the osteoporosis market and can generate blockbuster revenues. Such therapies answer the demand from patients and physicians for more convenient delivery mechanisms that increase compliance and ultimately improve treatment outcome.

Although bisphosphonates are the mainstay of osteoporosis treatment, there is potential for new and innovative products to gain market share. Those that suit niche populations, such as Chugai's ED-71 which finds favor as a vitamin D analogue in Japan, will be able to fight generic competition.

Reasons to Purchase

• Understand clinical and environmental unmet needs in the osteoporosis market based on key opinion leader comments
• Benchmark key late-stage pipeline products against the current market leader and class comparator
• Assess the global (US, Japan, five major EU) sales forecasts of key late-stage pipeline drugs; and examine their clinical and commercial potential

TABLE OF CONTENTS

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