August 2021: Belzutifan (Welireg, Merck), a hypoxia-inducible factor inhibitor, has been approved by the Food and Drug Administration for adult patients with von Hippel-Lindau disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumours (pNET) but do not require immediate surgery.
Belzutifan was studied in 61 patients with VHL-associated RCC (VHL-RCC) diagnosed based on a VHL germline change and at least one detectable solid tumour confined to the kidney in the ongoing Study 004 (NCT03401788), an open-label clinical investigation. Patients with other VHL-related malignancies, such as CNS hemangioblastomas and pNET, were enrolled. Belzutifan 120 mg was given to patients once a day until disease progression or intolerable toxicity.
The overall response rate (ORR) was the primary efficacy endpoint, as defined by radiological assessment and assessed by an independent review committee using RECIST v1.1. The duration of response (DoR) and time to response were two other efficacy goals (TTR). In individuals with VHL-associated RCC, an ORR of 49% (95 percent CI: 36, 62) was found. All patients with VHL-RCC who had a response were tracked for at least 18 months after treatment began. The median DoR was not met; 56% of respondents had a DoR of less than 12 months and an average TTR of 8 months. 24 patients with measurable CNS hemangioblastomas had an ORR of 63 percent, and 12 patients with measurable pNET had an ORR of 83 percent in patients with other VHL-associated non-RCC malignancies. For CNS hemangioblastomas and pNET, the median DoR was not met, with response durations of less than 12 months in 73 percent and 50 percent of patients, respectively.
Reduced haemoglobin, anaemia, fatigue, increased creatinine, headache, dizziness, elevated hyperglycemia, and nausea were the most prevalent adverse effects, including laboratory abnormalities, reported in almost 20% of patients who took belzutifan. Belzutifan usage can cause severe anaemia and hypoxia. Anemia was seen in 90% of participants in Study 004, with 7% having Grade 3 anaemia. Patients should be transfused as needed by their doctors. In individuals on belzutifan, the use of erythropoiesis stimulating drugs to treat anaemia is not suggested. Hypoxia occurred in 1.6 percent of patients in Study 004. Belzutifan can make some hormonal contraceptives ineffective, and it can harm an embryo or foetus if taken during pregnancy.
Belzutifan should be taken once a day, with or without food, in a dosage of 120 mg.
Check details here.