Rui Dai, Ning Lou, Xin Zheng, Xiaohong Han Clinical Pharmacology Research Center & Beijing Key Laboratory of Key Technologies for Early Clinical Trial Evaluation of Innovative Drugs for Major Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, Peopleâs Republic of ChinaCorrespondence: Xiaohong Han, Email hanxiaohong@pumch.cn Xin Zheng, Email zhengxin1@pumch.cnAbstract: Janus kinase inhibitors (JAKi) have undergone three decades of research and development, demonstrating substantial therapeutic efficacy and broad clinical applicability in autoimmune diseases, inflammatory disorders, hematopoietic malignancies, and a spectrum of rare diseases. However, their research and development are constrained by three key challenges: the difficulty in target selection and safety concerns arising from their effects on cellular signaling pathways, as well as the challenges in formulating optimal dosing regimens due to interindividual variability in pharmacokinetics. In this study, we systematically investigated the global development trends and pipeline evolution of JAKi from 1995 to 2025. A total of 271 JAKi candidates with 2035 associated clinical trials were identified to date. Clinical trial activity has risen rapidly since 2018 and remains robust. Phase III trials accounted for 26% of all studies, while 52% were in early-phase (Phase I/II) research, underscoring considerable potential for future development in this field. Immune-mediated inflammatory diseases and hematopoietic malignancies emerged as the leading therapeutic areas, representing 69.3% and 14.0% of all indications, respectively. Notably, rare diseases constituted 35.8% of the indications targeted by JAKi, with 20.4% of clinical trials focusing on these conditions. We comprehensively analyzed the multifaceted drivers underlying these developmental trends, with a specific emphasis on rare disease applications. Additionally, we critically evaluated the key challenges encountered in JAKi research and development, aiming to provide strategic insights to guide future investigations in this field.Keywords: JAK inhibitors, development trends, rare diseases
Dai et al. (Fri,) studied this question.