The Food and Drug Administration (FDA) has granted Priority Review to belzutifan for the potential treatment of patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC), not requiring immediate surgery.
“Von Hippel-Lindau disease is a rare genetic condition for which there is no systemic treatment option available and is associated with a high risk of cancer development in multiple organs,” said Dr Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “In fact, up to 70% of patients with VHL develop renal cell carcinoma during their lifetime.”
In patients with VHL disease, the accumulation of hypoxia-inducible factor-2 alpha (HIF-2α) can stimulate several oncogenes associated with cellular proliferation, angiogenesis and tumor growth. Belzutifan is a potent and selective inhibitor of HIF-2α.
The New Drug Application submission includes data from the phase 2 Study-004 trial (ClinicalTrials.gov: NCT03401788), an open-label study evaluating the efficacy and safety of belzutifan in patients with VHL disease who have at least 1 measurable RCC tumor. Belzutifan was administered orally once daily; patients were evaluated radiologically approximately 12 weeks after starting therapy, and every 12 weeks thereafter. Results showed a confirmed overall response rate (primary endpoint) of 36.1% (n=22/61; 95% CI, 24.2-49.4).
A Prescription Drug User Fee Act (PDUFA) date of September 15, 2021 has been set for the application review. Belzutifan is also being evaluated in phase 3 trials as monotherapy and as part of a combination regimen in previously treated patients and as a first-line treatment for advanced clear cell RCC.
Merck receives priority review from FDA for New Drug Application for HIF-2α inhibitor belzutifan (MK-6482). [press release]. Kenilworth, NJ: Merck; March 16, 2021.