Stakeholder Opinions: Osteoarthritis - Preconceptions Damage Awareness and Treatments

Table of Contents

About the CNS, Arthritis and Pain pharmaceuticalanalysis team

CHAPTER 1 EXECUTIVE SUMMARY

• Datamonitor insight into the osteoarthritis market
  • High unmet need and a large patient population are keydrivers towards research and innovation in osteoarthritis (OA), butageist perceptions and low awareness have a substantial negative impacton the market.
  • The need for a paradigm shift in the way osteoarthritisis treated has been suggested in the wake of drug controversy and thefailure of disease modifying approaches. Treatment currently centers onNSAID use, but following recent controversies, there is demand for analternative. However, many alternatives are battling against their ownpreconceptions. This currently adds to the drive for a disease-modifyingtreatment, but would be more successfully directed towards a holisticapproach.
  • Clinical trials for disease-modifying products for Oaare increasingly regulated and require careful design. However, the bestdesign for disease modification assessment has not yet been decided uponby experts. Advances in imaging offer promise for clinical trialend-points, but interpretation of results must be unified and newbiomarkers are being identified but are often difficult to utilize.

CHAPTER 2 INTRODUCTION AND EPIDEMIOLOGY

• Classifications
  • Primary (idiopathic) osteoarthritis
  • Secondary osteoarthritis
• Epidemiology of osteoarthritis
  • Country calculations
    • US population
    • European population
    • Japanese population
  • Radiographic hugely outweighs symptomatic jointinvolvement
  • Changes in the osteoarthritis population as the"baby boomer" generation reaches retirement age
  • Knee osteoarthritis usually assessed in trials andepidemiology studies but hip OA may offer an easier assessment target
  • Additional international osteoarthritis epidemiologystudies
    • Beijing OA study, China
    • Joint-replacement study, 2004, and the AustralianNational Health Survey, 1995
    • Prevalence of Rheumatic diseases in Greece: Across-sectional, population-based epidemiological study: The ESORDIGStudy, Andrianakos et al., 2003, 2005
  • Risk factors and patient-group segmentation are key inOA definition
    • Age
    • Gender
    • Mechanical stress
    • Obesity
• Treatment

CHAPTER 3 UNMET NEEDS

• Disease Modification is the key unmet need in OA
  • Restraints outweigh the current drivers for DMOADdevelopment
  • Clinical-trial design is challenging for both DMOADs andsymptom-modifying treatments as "gold-standard methods" arerapidly changing
  • Patient-group segmentation in clinical trials offers away to gain approval, but risks restricted use
• Quality of life and patient education should beaddressed for all treatments
• Osteoarthritis awareness and perception in societyreduces treatment uptake
  • Collaboration and dedicated government-funded researchorganization to aid this are the key to successful future OA treatment
  • The role of pharmaceutical companies
  • Direct to consumer advertising must be responsible inorder to change public perception
• Emerging imaging and biomarker research will impact bothdiagnosis and trial endpoints
  • Whole-organ MRI scoring system (WORMS): not perfect buta step forward
  • Biomarker research offers promise

CHAPTER 4 CURRENT TREATMENT CONTROVERSIES

• The Vioxx withdrawal is old news, but it still affectsphysician perception of osteoarthritis treatments
  • What is a Cox-2 inhibitor and should it still command ahigher price?
• Opioid use in osteoarthritis offers a good alternativeto NSAIDs, but "opioid-phobia" prevents high uptake
  • Topical opioids appear to break down perceptual barriers
• The impact of "professional patients" isincreasing in industry and government
• Non-pharmacological treatments are the first and thelast resort in osteoarthritis
  • Physiotherapy
  • Joint replacement
• Nutraceuticals, supplements and alternative therapyinvade the market
  • The Glucosamine/Chondroitin Arthritis Intervention Trial(GAIT)
  • The Glucosamine Unum In Die Efficacy Trial (GUIDE)
    • So does glucosamine work?
  • What can medical foods offer OA patients?
  • Is the competitive and profitable hyaluronic-acid marketbased on the placebo effect?

CHAPTER 5 PIPELINE DRUGS

• Pain- and inflammatory-relief pipeline treatments areparticularly diverse in mechanism
  • HCT 3012
  • Sativex
  • Licofelone
  • Botox
• Disease modifiers in OA are yet to progress past PhaseII
  • Matrix Metalloproteinase (MMP) inhibition
  • IL-1 inhibition
  • Enhancing cartilage repair
    • Autologous chondrocytes transplantation

CHAPTER 6 OPINION LEADER TRANSCRIPTS

• Contributing experts
  • Professor Howard Bird
  • Dr. Felix Eckstein
  • Dr. Robin Poole
  • Jane Tadman, Arthritis Research Campaign (ARC)
  • Professor Paul Dieppe
  • Cheryl Koehn, Arthritis Consumer Expert

CHAPTER 7 APPENDIX

• Bibliography
  • Websites
• The knee injury and osteoarthritis outcome score (KOOS)
• About Datamonitor
  • About Datamonitor Healthcare
  • Datamonitor Healthcares research and analysismethodologies
  • Datamonitor Healthcares therapy area capabilities
• Disclaimer

List of Tables

• Table 1: Estimated adult OA populations in the sevenmajor markets, by age group, 2006 (000s)
• Table 2: OA sufferers who present with the disease inspecific parts of the body (%): US, Japan and 5 EU markets, 2003
• Table 3: US OA patient population by age group andgender, 2006 (000s)
• Table 4: Breakdown of arthritis population from NHISsurvey and estimated OA percentages, 2003
• Table 5: Adult OA population in five major Eucountries, 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: Ukadults
• Table 8: Spanish EPISER study showing breakdown ofhand and knee OA by age group, 2001
• Table 9: Adult OA population in Japan, by age andgender, 2006 (000s)
• Table 10: Results of Framingham Heart Study/knee Oacohort, 1983-85
• Table 11: Results of Framingham Heart Study/knee Oacohort Follow-Up, 1992-93
• Table 12: Estimated US adult population and projectedprevalence of doctor-diagnosed arthritis and arthritis-attributableactivity limitations, among adults aged 18 years and older, US,2005-2030
• Table 13: Hip and knee OA patients in seven majormarkets (millions), 2006
• Table 14: WHO statistics for obesity and averagesystolic blood pressure in the seven major markets
• Table 15: Duragesic (fentanyl) trial results in OA,2005
• Table 16: GAIT study response rates by treatment groupand pain level, 2005
• Table 17: Pain and anti-inflammatory products inclinical trials for OA, 2006
• Table 18: Disease-modifying treatments for OA, 2006

List of Figures

• Figure 1: Adult (15+) OA population in the seven majormarkets, 2006
• Figure 2: Adult OA population, five major Eucountries, by age group, 2006
• Figure 3: Relationship between radiographic andsymptomatic OA
• Figure 4: Drivers of and impediments to DMOADdevelopment and their comparative importance and difficulty
• Figure 5: Opportunities and threats to companieswishing to enter the Cox-2 market
• Figure 6: Guidelines for selecting the appropriateNSAID in various clinical situations, 2006
• Figure 7: Effects of various NSAIDs on theconcentration of Cox-1 and Cox-2 in vitro
• Figure 8: US and UK knee and hip replacements,2000-2002
• Figure 9: Knee and hip replacement procedures per100,000 population, by country, 2000
• Figure 10: The knee injury and osteoarthritis outcomescore
• Figure 11: The knee injury and osteoarthritis outcomescore (cont.)