OA clinical trials: current targets and trials for OA. Choosing molecular targets: what have we learned and where we are headed?

Objective: The purpose of this article is to review the current status of drug development as it relates to both molecular targets and clinical trials for osteoarthritis (OA). Methods: A review of the literature in the context of currently what is known of the pathophysiology of OA and the learnings from past clinical trials is provided. Also discussed is the challenge of demonstrating efficacy and clinical benefit for pharmacologic interventions for OA in the context of current regulatory guidance documents for therapies for the treatment of OA. Results: There is a large unmet medical need for pharmacologic therapeutic interventions that modify the progression of OA and treat the symptoms associated with OA. The development of Disease Modifying OA Drugs (DMOADs) should take into account the current status of therapeutic interventions, as well as the various tissues that constitute the joint and contribute to joint mechanics, and the symptoms associated with structural changes. There is much to be learned about the pathophysiology of the joint that is currently poorly understood particularly as it relates to tissues other than hyaline articular cartilage. Improving our understanding that these tissues play in OA pathophysiology will likely yield treatment breakthroughs. Recently, tremendous progress has been made in the understanding of pain pathways with an emerging diversity of pain mechanisms and biology suggesting heterogeneity in pain etiology in OA. A multitude of new targets have been identified at the level of neuronal transduction/excitability, conduction, sensitization and transmission with multiple emerging compounds in development. Conclusions: The development of symptom modifying OA drug is exploding with a plethora of pain pathways being pursued and multiple candidates in advanced stages of clinical development. Structure modification in OA remains complex with significant development challenges. (C) 2009 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.