Belzutifan (Welireg™) is an oral small molecule inhibitor of hypoxia-inducible 
factor (HIF)-2α being developed by Peloton Therapeutics for the treatment of 
solid tumours, including renal cell carcinoma (RCC) with clear cell histology 
(ccRCC) and von Hippel-Lindau (VHL) disease-associated RCC. In August 2021, 
belzutifan received its first approval in the USA for the treatment of patients 
with VHL disease who require therapy for associated RCC, central nervous system 
(CNS) haemangioblastomas or pancreatic neuroendocrine tumours (pNET), not 
requiring immediate surgery. Clinical studies of belzutifan (as monotherapy or 
combination therapy) in other indications, including ccRCC, pNET and 
phaeochromocytoma/paraganglioma, are also underway in various countries. This 
article summarizes the milestones in the development of belzutifan leading to 
this first approval for certain VHL disease-associated tumours.