Zsuzsa Jenei-Lanzl, Svenja Maurer, Rolf E Brenner, Frank Zaucke, Michael Fuchs, Jana Riegger
{"title":"Emerging concepts and challenges in the development of disease-modifying osteoarthritis drugs - a more refined perspective.","authors":"Zsuzsa Jenei-Lanzl, Svenja Maurer, Rolf E Brenner, Frank Zaucke, Michael Fuchs, Jana Riegger","doi":"10.1007/s12272-025-01551-3","DOIUrl":null,"url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most common joint disease worldwide. Despite significant efforts byresearchers, no disease-modifying osteoarthritis drugs (DMOADs) have been approved yet. This review compares preclinical and clinical studies of promising therapeutic approaches to gain insights into the potential reasons for their failure in clinical trials. For this purpose, prime examples of different therapeutic groups, including the antioxidant NAC, senotherapeutic UBX0101, anti-inflammatory drug Anakinra®, Wnt inhibitor Lorecevivint®, chondroanabolic growth factor Sprifermin™, and various protease inhibitors, are discussed in detail. The limitations of commonly used OA animal models are elaborated to understand this failure better. Moreover, this review addresses the challenges of patient stratification into different endotypes and phenotypes, the consideration of subgrouping in clinical trials, and the lack of suitable clinical outcome parameters. In summary, this review highlights potential reasons for the high failure rate of DMOADs in clinical trials and outlines key points for future improvement.</p>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":" ","pages":""},"PeriodicalIF":6.9000,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Pharmacal Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12272-025-01551-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Osteoarthritis (OA) is the most common joint disease worldwide. Despite significant efforts byresearchers, no disease-modifying osteoarthritis drugs (DMOADs) have been approved yet. This review compares preclinical and clinical studies of promising therapeutic approaches to gain insights into the potential reasons for their failure in clinical trials. For this purpose, prime examples of different therapeutic groups, including the antioxidant NAC, senotherapeutic UBX0101, anti-inflammatory drug Anakinra®, Wnt inhibitor Lorecevivint®, chondroanabolic growth factor Sprifermin™, and various protease inhibitors, are discussed in detail. The limitations of commonly used OA animal models are elaborated to understand this failure better. Moreover, this review addresses the challenges of patient stratification into different endotypes and phenotypes, the consideration of subgrouping in clinical trials, and the lack of suitable clinical outcome parameters. In summary, this review highlights potential reasons for the high failure rate of DMOADs in clinical trials and outlines key points for future improvement.
期刊介绍:
Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.