The following is a summary of “FDA Approval Summary: Belzutifan for von Hippel-Lindau Disease–Associated Tumors” published in the November 2022 issue of Clinical Cancer by Fallah et al.

Belzutifan (WELIREG, Merck), a first-in-class hypoxia-inducible factor (HIF) inhibitor, was approved by the FDA on August 13, 2021, to treat adults with von Hippel-Lindau (VHL) disease who need therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET) but do not require immediate surgery. Clinically relevant improvements in overall response rate (ORR) were seen in patients participating in Study MK-6482-004, which led to FDA approval. 

Some of the 61 individuals additionally developed CNS hemangioblastomas and/or pNET in addition to their VHL-associated RCC. The median time to respond was 8 months, ORR was 49% (95% CI, 36-62), the median duration of response (DoR) was not met, and 56% of responders had a DoR of 12 months. CNS hemangioblastomas in 24 patients had an ORR of 63% (95% CI, 41-81) while pNET in 12 patients had an ORR of 83% (95% CI, 52-98). Although the median duration of response (DoR) was not reached, 73% of patients with CNS hemangioblastomas and 50% of patients with pNET had response durations of 12 months. 

About 20% or more of patients reported experiencing anemia, fatigue, elevated creatinine, headache, dizziness, elevated glucose, or nausea as their primary adverse reaction. In addition, some hormonal contraceptives may become ineffective when taking belzutifan, and it may also harm developing embryos and fetuses if taken during pregnancy. This article provides a concise summary of the evidence and FDA reasoning for the standard approval of belzutifan for this indication.