FDA Approves Belzutifan For Adults With Von Hippel-Lindau Related Cancers

Belzutifan, a hypoxia-inducible factor inhibitor, has been approved for treatment of adults with cancers related to von Hippel-Lindau disease.

The FDA approved belzutifan (Welireg) to treat adult patients with von Hippel-Lindau (VHL)- associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNETs), who do not require immediate surgery, according to a release issued by the agency.

The regulatory decision was based off updates from the ongoing, open label Study 004 trial (NCT03401788) that evaluated the hypoxia-inducible factor inhibitor in 61 patients with VHL-RCC. To be eligible, patients had to have a VHL germline alteration and at least 1 solid tumor localized to the kidney. Participants with VHL-related tumors like CNS hemangioblastomas and pNETs were also included.

Patients were administered 120 mg oral belzufitan once daily until progressive disease or intolerable toxicity.

Primary efficacy end points include overall response rate (ORR), duration of response (DOR), and time-to-response (TTR). ORR will be assessed via radiology assessment and an independent review committee in accordance with RECIST v1.1 criteria. Current data show an ORR of 49% (95% CI, 36-62) for patients with VHL-RCC, 63% for patients with CNS hemangioblastomas, and 83% for patients with measurable pNETs.

Median DOR has not been reached. Patients with VHL-RCC were followed for a minimum of 18 months from treatment initiation, and 56% of responders experienced a DOR greater or equal to 6 months. The median TTR in this group was 8 months. Among the CNS hemangioblastoma cohort, 73% of responders experienced a DOR of ≥12 months, as did 50% of responsive patients in the pNET group.

Adverse events (AEs) reported in the study included laboratory abnormalities, decreased hemoglobin, anemia, fatigue, increased creatinine, headache, dizziness, increase glucose, and nausea. Nurses should be aware that the anemia and hypoxia associated with belzutifan use can be severe. In total, 90% of patients in the study experienced anemia and 7% reported the severity of their anemia to be grade 3. In addition, 1.6 % of patients experienced hypoxia.

Erythropoiesis stimulating agents are not recommended in patients treated with belzutitfan. Investigators reported that belzutifan renders some hormonal contraceptives infective and that the drug can inflict embryo-fetal harm.


FDA approves belzutifan for cancers associated with von Hippel-Lindau disease. FDA. News release. Accessed August 13, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-cancers-associated-von-hippel-lindau-disease?utm_medium=email&utm_source=govdelivery