変形性関節症動向

Abstract

Overview

Introduction

Osteoarthritis (OA) is characterized by the progressive destruction of articular joints and is a major cause of pain in Western populations. OA is the most common form of arthritis and severely impacts on the physical function and day-to-day quality of life of an individual. OA also impacts heavily on the economy and it is believed to cost the US an estimated $60 billion per year.

Scope

• Detailed pipeline analysis of the key products in development for OA, plus indication specific drug sales forecasts to 2015
• Late-phase pipeline drug competitive analysis based on clinical and commercial attractiveness
• Overview of patient potential and unmet needs in OA across the US, 5EU and Japanese markets
• Identification of licensing opportunities based on company portfolio and market needs

Report Highlights

The issue of cardiovascular safety remains at the forefront of the COX-2 and traditional NSAID classes. As evidenced by Prexige (lumiracoxib) and Arcoxia (etoricoxib), appropriately designed, large-scale safety studies will be crucial if any COX-2s are to be approved by the FDA and EMEA. Prexige and Arcoxia remain in pre-registration in the US.

Over the next ten years a number of COX-2 inhibitors as well as NSAIDs and corticosteroids, some with novel mechanisms of action and reportedly improved side effect profiles, will enter the market. Success will depend on effective but restrained marketing, product differentiation and strategic out-licensing arrangements.

Over the next ten years a number of COX-2 inhibitors as well as NSAIDs and corticosteroids, some with novel mechanisms of action and reportedly improved side effect profiles, will enter the market. Success will depend on effective but restrained marketing, product differentiation and strategic out-licensing arrangements.

Reasons to Purchase

• Understand the potential of COX-2s such as Novartis' Prexige and Merck's Arcoxia in the OA indication.
• Quantify the future size and potential of the market for novel treatments in the OA indication.
• Identify who the key players in the OA market will be as well as understanding gaps in the market for potential products.

Table of Contents

• ABOUT DATAMONITOR HEALTHCARE
  • About the CNS, Arthritis and Pain pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of the analysis
  • Datamonitor insight into the osteoarthritis market
    • Summary
  • Key metrics
  • Datamonitor pipeline assessment summary
• CHAPTER 2 PATIENT POTENTIAL
  • Definition of osteoarthritis
  • Segmentation of osteoarthritis
    • Primary (idiopathic) osteoarthritis
    • Secondary osteoarthritis
  • Epidemiology of osteoarthritis
    • Country calculations
      • OA affects 11% of the adult US population
      • OA will be a growing problem as the elderly European population increases
      • OA of the knee affects 70% of the Japanese OA population
  • Unmet need in OA
    • Disease modification is the key unmet need in OA
    • OA drugs require a reduced side effect profile
    • Quality of life and patient education should be addressed for all treatments
    • OA awareness and perception in society requires improvement
    • Emerging imaging and biomarker research will impact both on diagnosis and trial endpoints
• CHAPTER 3 R&D APPROACH
  • Classification of marketed and pipeline OA drugs
    • Non-steroidal anti-inflammatory drugs (NSAID)
    • Disease modifiers (DM)
      • DMOADs
      • Growth factors and hormones
      • Cell therapy and gene therapy
    • Analgesics
    • Corticosteroids (CS)
    • Hyaluronic acids (HA)
    • Nutriceuticals
  • Clinical trial design in osteoarthritis
    • Comparator Drugs
      • The choice of comparator drug is vital to ensure OA trial reliability
      • The FDA requires the use of naproxen as the comparator drug in long-term safety studies in OA
  • Clinical trial endpoints in OA
    • Pain scale endpoints
      • Western Ontario and McMaster Osteoarthritis (WOMAC) Index remains the most widely used clinical trial endpoint
      • Australian/Canadian (AUSCAN) Index is used specifically in clinical trials of hand OA
      • Lequesne's Algofunctional Indices
      • OARSI/OMERACT Response Criteria aim to improve responder criteria in clinical trials but needs better validation
    • Disease modification endpoints
      • Radiography remains the most widely used endpoint in DMOAD trials but accuracy is questionable
      • Magnetic Resonance Imaging is a powerful but costly tool for monitoring disease progression in articular joints
      • Biomarkers are still under investigation and require further validation
    • Other endpoints
      • Anti-Platelet Trialists' Collaboration (APTC) is a useful endpoint to assess the CV risk of COX-2s
• CHAPTER 4 OSTEOARTHRITIS PIPELINE ANALYSIS
  • Pipeline overview
    • Pre-registration
    • Phase III
    • Phase II
  • Key companies involved in the osteoarthritis pipeline
    • Pfizer dominates the OA market with Celebrex, but will it be first to market with a DMOAD?
      • Celebrex is the market leading COX-2 inhibitor and has achieved blockbuster status
      • Pfizer has two DMOAD candidates in Phase II development
      • Pfizer buys Rinat Neuroscience to extend neuroscience research and in doing so acquires a product candidate for OA
    • NicOx expects naproxcinod to compete with COX-2 inhibitors
      • NicOx has developed clear strategies for success
    • Overview of strategies for success
• CHAPTER 5 NSAID LATE-STAGE DRUG ANALYSIS & FORECASTS
  • Overview for NSAIDs
    • Pipeline summary
  • Definition of current NSAID comparator therapy
  • Lumiracoxib
    • Drug overview
    • Clinical trial data
      • Study 1
      • Study 2
      • Study 3
    • Patient potential
      • Prexige will be an attractive treatment option for OA, and has been shown to be as safe as ibuprofen and naproxen
    • Marketing factors
      • Novartis is in a good position to market Prexige with strong safety data and significant market experience
    • Satisfaction of unmet needs
      • The FDA has concluded that Prexige carries only a moderate CV risk, similar to Pfizer's Celebrex
    • Forecasts to 2015
  • Etoricoxib
    • Drug overview
    • Clinical trial data
      • Study 1
      • Study 2
      • Study 3
    • Patient potential
      • Merck is enrolling unprecedented numbers of OA patients on the MEDAL trial to investigate the CV safety of Arcoxia
      • Arcoxia has a limited patient potential, however, there is a possibility that a niche market for Arcoxia exists in patients who found relief from Vioxx
    • Marketing factors
      • It would be inadvisable for Merck to market Arcoxia in a similar fashion as seen previously with Vioxx
    • Satisfaction of unmet needs
      • Arcoxia carries a high cardiac risk and the EMEA recommends that Arcoxia be contra-indicated in patients with hypertension
    • Forecasts to 2015
  • Naproxcinod (AZD3582)
    • Drug overview
    • Clinical trial data
      • Study 1
      • Study 2
      • Study 3
    • Patient potential
      • Naproxcinod will gain from the anxieties that surround the COX-2s
    • Marketing factors
      • NicOx needs to secure a marketing partner for naproxcinod
    • Satisfaction of unmet needs
      • Naproxcinod has an improved safety profile over other NSAIDs and COX-2s
      • Naproxcinod may have a niche market in OA patients with hypertension and increased CV risk
    • Forecasts to 2015
  • Licofelone
    • Drug overview
    • Clinical trial data
      • Study 1
      • Study 2
    • Patient potential
      • Licofelone has similar efficacy to NSAIDs and COX-2s but its long-term safety still needs to be assessed
    • Marketing factors
      • EuroAlliance need to secure a new global marketing agreement to ensure the success of licofelone
    • Satisfaction of unmet needs
      • Hepatic tolerability could help differentiate Licofelone from Celebrex
    • Forecasts to 2015
  • IDEA-033
    • Drug overview
    • Clinical trial data
      • Study 1
      • Study 2
    • Patient potential
      • Topical IDEA-033 could be a safe and effective alternative to oral NSAIDs and COX-2s
    • Marketing factors
      • Idea Therapeutics lacks experience of the OA market and requires a marketing partner
    • Satisfaction of unmet needs
      • IDEA-033 has a reduced potential for side effects because of low systemic concentrations of ketoprofen
    • Forecasts to 2015
  • GW-406381
    • Drug overview
    • Clinical trial data
      • Study 1
    • Patient potential
      • As measured by WOMAC subscore, GW-406381 is more effective than Celebrex at improving pain in OA
    • Marketing factors
      • GW-406381 has a similar effect on blood pressure as Celebrex
    • Satisfaction of unmet needs
      • The commercial attractiveness of GW-406381 will be significantly reduced because it will have fourth to market status
    • Forecasts to 2015
  • LAS-34475
    • Drug overview
    • Clinical trial data
      • Study 1
    • Patient potential
      • The patient potential for LAS-34475 will not be as great as the potential seen with previous COX-2 inhibitors
    • Marketing factors
      • LAS-34475 will benefit from Almirall's previous experience of the OA market
    • Satisfaction of unmet needs
      • LAS-34475 requires a long-term safety study
      • Fifth to market status will damage LAS-34475's commercial attractiveness
    • Forecasts to 2015
  • Other late stage NSAIDs
    • Efipladib
      • Phospholipase inhibitors are not specific and would be more interesting in truly inflammatory arthritis
    • PN 100
      • Combination therapies, such as PN 100, ensure patient compliance
    • SFPP
      • Mitsubishi Pharmaceuticals pulls out of SFPP development
  • Late-stage development compounds recently discontinued
    • Tilmacoxib
    • AZD-9056
• CHAPTER 6 DISEASE MODIFIER LATE-STAGE DRUG ANALYSIS
  • Overview for disease modifiers
  • Definition of current comparator therapy
  • ChondroCelect
    • Overview
      • ChondroCelect is a cell therapy for the treatment of cartilage damage in OA
      • ChondroCelect began the TiGenix Phase III clinical trial (TIGACT-01) in 2005
  • Salmon Calcitonin
    • Drug overview
      • Salmon calcitonin could prevent the enhanced turnover of bone that is associated with OA progression but osteoporosis appears to be the primary indication
      • Salmon calcitonin has a good safety profile and is not carcinogenic
    • Clinical trial data
  • Doxycycline
    • Drug overview
    • Clinical trial data
  • Other disease modifiers
    • Anakinra
      • Anakinra improves WOMAC pain subscore but the improvement is not statistically significant
    • Adalimumab
      • Pilot studies at Universities are underway for Humira in OA
    • SD-6010
      • Pfizer sees iNOS as a potential therapeutic target
    • CP-544439
      • Pfizer's CP-544439 specifically targets MMP-13
    • AZD-8955
    • CPA-926
  • Late-stage development compounds recently discontinued
    • Pralnacasan
    • AMG-108
    • S-3536
    • ONO-4817
    • ICE Inhibitors
    • AD-729
• CHAPTER 7 ANALGESICS LATE-STAGE DRUG ANALYSIS & FORECASTS
  • Overview for analgesics
    • Pipeline summary
  • Current comparator therapy: Acetaminophen
  • Zucapsaicin
    • Drug overview
    • Clinical trial data
    • Patient potential
      • Zucapsaicin will be limited to OA patients who do not tolerate or whose pain is not controlled by NSAIDs or COX-2s
    • Marketing factors
      • Winston Laboratories does not have experience in the OA market and requires a partner for zucapsaicin
    • Satisfaction of unmet needs
      • The future long-term safety trial for zucapsaicin will help clarify a reduced side effect profile
    • Forecasts to 2015
  • Other analgesic drugs
    • AT-1022
      • AT-1022 is a hydromorphone patch that has been specifically designed to provide sustained levels of analgesia
    • RN-624
      • RN-624 is a first in class biologic therapy for the treatment of the pain associated with OA
      • Clinical trial data
    • Bicifadine
      • With sustained release bicifadine, OA patients will experience less frequent daily dosing and an increased tolerability of the drug
      • Clinical trial data
    • MK-0686
      • Merck has not disclosed the mode of action of MK-0686
    • Icatibant
      • Icatibant is a selective bradykinin B2 receptor antagonist
• CHAPTER 8 CORTICOSTEROID LATE-STAGE DRUG ANALYSIS & FORECASTS
  • Overview for corticosteroids
  • Definition of current comparator therapy
  • CRx-102
    • Drug overview
    • Clinical trial data
      • Study 1
    • Patient potential
      • CRx-102 will have a greater patient potential than the gold standard corticosteroid prednisolone
    • Marketing factors
      • CombinatoRx has collaborations and agreements with pharmaceutical companies for some of its product candidates but requires a partner for CRx-102
    • Satisfaction of unmet needs
      • CRx-102 is a well tolerated drug, which has a reduced side effect profile
    • Forecasts to 2015
• CHAPTER 9 INNOVATIVE EARLY-STAGE PROJECTS
  • Overview for innovative early-stage projects
    • Phase I
    • Preclinical
  • MMP inhibitors
    • MMP-1 and MMP-13 are key targets for future OA therapies
    • Most early-stage DMOADs are directed against MMPs but side effects are an issue
  • Tumor necrosis factor and Interleukin-1
    • TNF-alpha and IL-1 antagonists offer promise but problems such as short half life remain an issue
  • Cathepsin K inhibitors
    • Cathepsin K inhibitors are being developed by GSK and Medivir
  • Bone modulators
    • Preventing the loss of bone in OA could slow or stop disease progression
  • c-fms inhibitors
    • GSK is looking to treat OA by inhibiting inflammatory cells
  • Botox
    • Intra-articular Botox injections might provide pain relief in OA but unwanted effects on surrounding muscle might become evident
  • NFKappaB modulators and IKK beta inhibitors
    • Therapies targeting gene transcription raise concerns over potential side effects
  • Key research impacts on osteoarthritis
• APPENDIX A
  • Methodology
    • Datamonitor forecast methodology
      • ICD10 code definition of OA indication
      • Product forecasts
      • Definition of a standard unit
  • Contributing experts
  • Bibliography
    • Websites
    • Datamonitor reports
  • Report methodology
• APPENDIX B
  • About Datamonitor
    • About Datamonitor Healthcare
  • Datamonitor Healthcare's therapy area capabilities
    • About the CNS, Arthritis and Pain analysis team
    • Disclaimer
  • List of Tables
    • Table 1: Estimated adult OA populations in the seven major markets, by age group, 2006 (000s)
    • Table 2: OA sufferers who present with the disease in specific parts of the body (%): US, Japan and 5EU markets, 2003
    • Table 3: US OA patient population by age group and gender, 2006 (000s)
    • Table 4: Breakdown of arthritis population from NHIS survey and estimated OA percentages, 2003
    • Table 5: Adult OA population in five major EU countries, by age and gender, 2006 (000s)
    • Table 6: Combined sample of northern England studies, radiographic knee OA by age and gender
    • Table 7: Estimated symptomatic knee OA prevalence: UK adults
    • Table 8: Spanish EPISER study showing breakdown of hand and knee OA by age group, 2001
    • Table 9: Adult OA population (000s) in Japan, by age and gender, 2006
    • Table 10: GAIT study response rates by treatment group and pain level, 2005, %
    • Table 11: Baseline Lequesne and WOMAC, with 6-month ITT changes and % of OARSI-A responders in the GUIDE study
    • Table 12: Biomarkers in OA
    • Table 13: Pipeline drugs in pre-registration development for OA, 2006
    • Table 14: Pipeline drugs in Phase III development for OA, 2006
    • Table 15: Pipeline drugs in Phase II development for OA, 2006
    • Table 16: Number of key OA therapies by class and phase of development, 2006
    • Table 17: Pipeline OA therapies by mode of delivery, 2006
    • Table 18: NicOx R&D pipeline, 2006
    • Table 19: Key NSAIDs in late-stage R&D pipeline for OA, 2006
    • Table 20: Aleve's key facts, 2006
    • Table 21: Lumiracoxib TARGET study: summarized GI safety results
    • Table 22: Lumiracoxib TARGET study: summarized CV safety results,
    • Table 23: Lumiracoxib vs celecoxib: WOMAC total score.
    • Table 24: Lumiracoxib vs celecoxib: VAS total score.
    • Table 25: Factors having an impact on Prexige's sales revenue across the seven major markets, 2006-15
    • Table 26: Cost per standard unit for COX-2s in the UK
    • Table 27: Factors having an impact on Arcoxia's revenue 2006-15
    • Table 28: Difference between groups in the change in WOMAC pain subscale score (mm) from baseline to the mean of weeks 4 and 6.
    • Table 29: Factors having an impact on naproxcinod's revenue from launch-2015
    • Table 30: Change from baseline in liver enzyme levels at week 12 for licofelone and celecoxib
    • Table 31: Factors having an impact on licofelone's revenue from launch-2015
    • Table 32: Factors impacting IDEA-033's revenue from launch-2015
    • Table 33: GW-406381 vs celecoxib: Effect on systolic blood pressure
    • Table 34: Factors having an impact on GW-406381's revenue from launch-2015
    • Table 35: LAS-34475: OARSI criteria results, EULAR 2003
    • Table 36: Factors having an impact on LAS-34475's revenue from launch-2015
    • Table 37: Discontinued R&D projects in NSAIDs, 2003-06
    • Table 38: Key disease modifiers in late-stage R&D pipeline for OA, 2006
    • Table 39: Results of a Phase II efficacy trial for oral salmon calcitonin
    • Table 40: Results of doxycycline vs placebo on JSN
    • Table 41: Discontinued R&D projects in DMOADs, 2003-06
    • Table 42: Key analgesics in late-stage R&D pipeline for OA, 2006
    • Table 43: Factors having an impact on zucapsaicin's revenue from launch-2015
    • Table 44: RN-624: Results of Phase I study
    • Table 45: Key products in late-stage R&D pipeline for corticosteroids, 2006
    • Table 46: CRx-102: Phase II clinical trial results, 2006
    • Table 47: Factors having an impact on CRx-102's revenue from launch-2015
    • Table 48: Phase I and preclinical molecular targets for disease modifying therapies, 2006
    • Table 49: Pipeline drugs in Phase I development for OA, 2006
    • Table 50: Pipeline drugs in preclinical development for OA, 2006
    • Table 51: Datamonitor's definition of OA market by ICD10 code
    • Table 52: Datamonitor's forecast OA revenues of pipeline drugs across the seven major markets ($m)
    • Table 53: Calculation of the $/SU of Celebrex and Arcoxia for Japan based on average historic sales in Pacific Rim from 2002 - 2005
  • List of Figures
    • Figure 1: The OA market, 2006-2015
    • Figure 2: Comparative sales revenue for key OA pipeline products in the seven major markets, US$, m, 2006-2015
    • Figure 3: Drug OA drug assessment summary
    • Figure 4: Adult (15+) OA population in the seven major markets, 2006
    • Figure 5: Adult OA population, five major EU countries, by age group, 2006
    • Figure 6: Key unmet needs in OA, 2006
    • Figure 7: Number of key OA therapies by class and phase of development, 2006
    • Figure 8: Pfizer's therapeutic focus, 2005
    • Figure 9: Total vs OA-specific historical sales of Celebrex in the US
    • Figure 10: Total historic sales and OA-specific sales of Bayer's Aleve in the US, 2002 - 2005
    • Figure 11: Datamonitor's competitive positioning analysis of Prexige for OA, 2006
    • Figure 12: Comparison of IC50s of NSAIDs and COX-2 inhibitor
    • Figure 13: Datamonitor's forecast of OA sales for Prexige across the seven major markets (US$m), 2006-2015
    • Figure 14: Datamonitor's competitive positioning analysis of Arcoxia for OA, 2006
    • Figure 15: Datamonitor's forecast of OA sales for Arcoxia across the seven major markets (US$m), 2006-2015
    • Figure 16: Datamonitor's competitive positioning analysis of naproxcinod for OA, 2006
    • Figure 17: Datamonitor's forecast of OA sales for naproxcinod across the seven major markets (US$m), 2006-2015
    • Figure 18: Datamonitor's competitive positioning analysis of licofelone for OA, 2006
    • Figure 19: Datamonitor's forecast of OA sales for licofelone across the seven major markets (US$m), 2006-2015
    • Figure 20: Datamonitor's competitive positioning analysis of IDEA-033 for OA, 2006
    • Figure 21: Datamonitor's forecast of OA sales for IDEA-033 across the seven major markets (US$m), 2006-2015
    • Figure 22: GW-406381: Phase II study design
    • Figure 23: GW-406381: Improvement in WOMAC subscore
    • Figure 24: Datamonitor's competitive positioning analysis of GW-406381 for OA, 2006
    • Figure 25: Datamonitor's forecast of OA sales for GW-406381 across the seven major markets (US$m), 2006-2015
    • Figure 26: Datamonitor's competitive positioning analysis of LAS-34475 for OA, 2006
    • Figure 27: Datamonitor's forecast of OA sales for LAS-34475 across the seven major markets (US$m), 2006-2015
    • Figure 28: Datamonitor's competitive positioning analysis of zucapsaicin for OA, 2006
    • Figure 29: Datamonitor's forecast of OA sales for zucapsaicin across the seven major markets (US$m), 2006-2015
    • Figure 30: CRx-102: Primary endpoint results for Phase II study
    • Figure 31: Datamonitor's competitive positioning analysis of CRx-102 for OA, 2006
    • Figure 32: Datamonitor's forecast of OA sales for CRx-102 across the seven major markets (US$m), 2006-2015