Advances and Challenges in the Pursuit of Disease-Modifying Osteoarthritis Drugs: A Review of 2010-2024 Clinical Trials.

: Osteoarthritis (OA) is a highly prevalent, degenerative joint disease capable of causing severe pain and impaired mobility. Current treatments mitigate symptoms but do not cure the disease. The development of a disease-modifying osteoarthritis drug (DMOAD) could improve patient outcomes by slowing, halting, or reversing joint damage. Many DMOADs have progressed to clinical trials, but very few have made a significant impact, and none have been approved for clinical use. The purpose of this review is to present an update on the current status of DMOADs with a particular focus on results published since 2010. : A comprehensive search was conducted within PubMed and ClinicalTrials.gov for novel DMOADs enrolled in phase II and III clinical trials between 1 January 2010 and 1 July 2024. : Eleven DMOAD candidates are reviewed and critically analyzed for their potential benefit in OA treatment-Lorecivivint (SM04690), TissueGene-C, Cindunistat (SD-6010), Sprifermin, UBX0101, TPX-100, GLPG1972/S201086, Lutikizumab (ABT-981), SAR113945, MIV-711, and LNA043-and relevant challenges to their development are discussed. : Six DMOADs have demonstrated statistically significant evidence of a structural or symptomatic benefit without major safety concerns in phase II and III randomized controlled trials post-2010.