FDA Approves Belzutifan for Cancers Associated With von Hippel-Lindau Disease

The use of belzutifan has been approved by the FDA for patients with cancer that is associated with von Hippel-Lindau disease who do not need immediate surgery.

The FDA has approved the use of belzutifan (MK-6482) for cancers associated with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNETs) that do not need immediate surgery, according to a press release from the FDA.1

Thus far, patients with VHL-associated RCC experienced an overall response rate (ORR) of 49% (95% CI, 36%-62%). All patients who experienced a response were monitored for a minimum of 18 months from the start of their treatment with belzutifan. Although the median duration of response (DOR) was not reached, 56% of responders had a DOR of 12 months or more, as well as a median time to relapse of 8 months. Additionally, patients with measurable CNS tumors (n = 24) had an ORR of 63% and the pNET cohort (n = 12) had an ORR of 83%. Similarly, the median DOR was not reached and 73% and 50% of both groups, respectively, had a response lasting 12 months or more.

The agent is currently under investigation as part of the ongoing open-label Study 004 (NCT03401788), which enrolled 61 patients with VHL-associated RCC, as well as enrolling patients with other VHL tumors, including CNS and pNET. Patients received 120 mg of belzutifan once daily until experiencing disease progression or unacceptable toxicity.

The most common adverse effects in patients who were treated with the hypoxia-inducible factor inhibitor included decreased hemoglobin, anemia, fatigue, increased creatinine, headache, and dizziness. Notably, anemia and hypoxia associated with treatment with belzutifan can be severe. Seven percent of patients developed grade 3 anemia. Additionally, the use of erythropoiesis stimulating agents to treat anemia in patients who have been treated with belzutifan is not recommended.


FDA approves belzutifan for cancers associated with von Hippel-Lindau disease. News release. FDA. August 13, 2021. Accessed August 13, 2021. https://bit.ly/37DMnzV