Small-Molecule Drugs Approved by the FDA in 2025.
Wang Xiaoyue X, Wang Ying Y, Luo Rui R, Niu Donghai D et al.
In today's pharmaceutical sector, innovation is not only the core driver of industry upgrading, but also closely tied to patient health and well-being. A drug's innovative mechanism of action, physiological effects, chemical structure, and indications collectively reflect both its clinical therapeutic value and the novelty of underlying basic research. This article presents the innovative advances of 31 small-molecule drugs (accounting for 67.4%) approved by the U.S. Food and Drug Administration (FDA) in 2025. These therapeutics span multiple therapeutic areas, including oncology, autoimmune diseases, infectious diseases, cardiovascular disorders, and metabolic conditions, and target a diverse array of molecular targets such as mitogen-activated protein kinase kinases 1 and 2 (MEK1/2), colony-stimulating factor 1 receptor, protein tyrosine kinase Tec, and Bruton tyrosine kinase, among others. Among these approved small-molecule drugs, 13 are designated as "first-in-class" therapies, reflecting the continuous innovation in the field of new drug development. Notably, many of these drugs (e.g., Journavx, Brinsupri, Jascayd, and Kygevvi) have also been granted breakthrough therapy designation, which underscores that they not only feature novel mechanisms of action, but also deliver clinically meaningful efficacy advantages over prior therapeutic options. Notably, in 2025, the FDA approved sunvozertinib, a novel small-molecule drug independently developed by Dizal (Jiangsu, China) Pharmaceutical Co., Ltd., for locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, contributing Chinese wisdom and solutions to the transformative evolution of global drug development paradigms. Cross-technology integration, long-acting drug delivery, and precision medicine stand as core industrial trends, enabling innovative drugs to boost therapeutic efficacy, mitigate toxic side effects and refine patients' medical experience, offering patients expanded regimens for improved survival outcomes. With the development of first-in-class drugs, therapies targeting previously undruggable targets-or those inaccessible via conventional approaches-are entering clinical practice, creating major opportunities for novel, mechanism-based drug discovery. This article comprehensively analyzes the mechanisms of action, synthesis methods, and clinical trials of these drugs chronologically, and delineates emerging trends in novel drug development.