Disease Modifying Osteoarthritis Drugs - The Search for the 'Holy Grail' Continues

Table of Contents

EXECUTIVE SUMMARY

Introduction

Scope and coverage of the Brief

Key findings about the topic

SECTION 1 INTRODUCTION

Epidemeology

Current treatments available

What is required of a DMOAD?

Clinical trial design for DMOADs

Measuring the outcome

Radiography

Other methods

Biomarkers

Cleaved Type II collagen molecules

New collagen synthesis

Protoglycan aggrecan

COMP (Cartilage oligomeric matrix protein)

Bone

Pain Scales

Drug delivery

Ethnic differences in response

SECTION 2 DMOADS IN THE PIPELINE

Preventing cartilage degradation

Overview table

Matrix Metalloproteinase (MMP) Inhibition

Doxycycline – Indiana University – Phase II

Oral MMP inhibitor - P&G - Pre-clinical

CMT-3 – Collagenex – Discovery

Esculetin – National Defense College, Japan – Pre-clinical

Interleukin –1 (IL-1) inhibition

Kineret – Amgen – Phase I

Diacerein - University Rene Descartes, France – PII

Insulin

Slow release Insulin – Genentech – Pre-clinical

Steroidal compounds

DHEA – Seoul National University Hospital – Pre-clinical

Enhancing cartilage repair

Overview table

Growth factors

Transforming Growth Factor (TGF)

Insulin-like Growth Factor (IGF-1)

Biomechanical and tissue engineering technologies

Autologous chondrocyte transplantation (ACT)

Polymer scaffold - Rice University/ NIH - Pre clinical

BST-CarGel – Biosyntech – Phase I

Chondrogen – Osiris – Pre-clinical

Other mechanisms

Overview table

Photodynamic treatment

Electromagnetic fields

Glucosamine and Chondroitin Sulphate (GCS)

Estrogen

Estrogen receptors

Conclusions

Discontinued trials

MMP inhibitor (BAY 12-9566) – Bayer – PII discontinued

Insulin Growth Factor (IGF) – Chiron – PII discontinued

SECTION 3 COMPARISON OF DMOAD METHODS

DMOAD deadlock

Comparison of technologies

APPENDIX

Contributing experts

Bibliography

Epidemiology

Clinical trial design

Clinical trial data

Research methodology

Disclaimer

List of Tables

Table 1: OA current and future estimated prevalence by country, 2003 and 2010

Table 1: Combination and monotherapies, in the seven major markets, %, 2003

Table 2: Pros and cons of other end-point measurement methods

Table 3: DMOADs using the cartilage degradation prevention mechanism, 2003

Table 4: Pain responses in knee OA after a single intra-articular injection of Kineret (anakinra)

Table 5: Cartilage repair enhancing drugs or technology, 2003

Table 6: ACT trials from the Journal of Bone and Joint Surgery, 2003

Table 7: Other mechanisms of disease modification, 2003

Table 8: Summary of DMOADs in development

List of Figures

Figure 1: Combination and monotherapies, in the seven major markets, 2003

Figure 2: Cartilage remodeling

Figure 3: Generation of some of the cartilage biomarkers

Figure 4: Constraints and drivers of DMOAD development

Figure 5: Comparison of products addressing the balance of cartilage degradation or repair, 2003