What is the use of Belzutifan in medical treatment?

From the Guidelines

Belzutifan is used in the medical treatment of renal cell carcinoma (RCC), specifically for patients with von Hippel-Lindau (VHL)-associated RCC and as an alternative option for patients who have progressed on VEGF/PD-1-targeted combination therapy.

Key Uses of Belzutifan

• VHL-associated RCC: Belzutifan is a novel hypoxia-inducible factor 2a transcription factor inhibitor that has shown an overall response rate (ORR) of 64% in patients with VHL-associated RCC, reducing the need for subsequent intervention 1.
• Second-line treatment: Belzutifan is an option for second-line therapy after progression on VEGF/PD-1-targeted combination therapy, although alternatives such as cabozantinib may be preferable 1.
• Third-line treatment: Belzutifan has a PFS advantage over everolimus in heavily pretreated patients with ccRCC and should be used instead of everolimus in this setting 1.

Important Considerations

• FDA approval: Belzutifan has been approved by the FDA for the medical control of primary VHL-associated renal cell carcinomas 1.
• Sequencing therapy: Sequencing VEGFR-targeted therapy is an alternative to belzutifan and may be beneficial in advanced RCC 1.
• Toxicity and quality of life: Belzutifan has been shown to have favorable toxicity and quality-of-life profiles compared to everolimus 1.

From the FDA Drug Label

1. 1 Mechanism of Action Belzutifan is an inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α). HIF-2α is a transcription factor that plays a role in oxygen sensing by regulating genes that promote adaptation to hypoxia. In vivo, belzutifan demonstrated anti-tumor activity in mouse xenograft models of renal cell carcinoma.

The use of Belzutifan in medical treatment is as an inhibitor of hypoxia-inducible factor-2α (HIF-2α), which plays a role in oxygen sensing and regulating genes that promote adaptation to hypoxia. It has demonstrated anti-tumor activity in mouse xenograft models of renal cell carcinoma. 2

From the Research

Medical Use of Belzutifan

• Belzutifan is used for the treatment of renal cell carcinoma (RCC), particularly in patients with von Hippel-Lindau (VHL) disease 3, 4, 5.
• It is the first FDA-approved drug to target hypoxia-inducible factor 2 alpha (HIF-2α), preventing the transcription of downstream oncogenes 3.
• Belzutifan has demonstrated activity in clinical trials as a front- and later-line therapy, and in combination with tyrosine kinase inhibitors 3, 5.
• It has been largely well tolerated, although anemia represents a common on-target side effect, along with hypoxia, which requires monitoring during treatment 3, 4, 5, 6.

Specific Indications

• Belzutifan is approved for treating clinical manifestations of VHL disease, including RCC 3.
• It is also approved for treating advanced sporadic RCC that has progressed through multiple lines of treatment 3.
• Belzutifan has shown benefit in VHL-associated tumors, including hemangioblastomas of the brain and spine, with a 30% response rate and ~30%-50% reduction in tumor size 6.

Ongoing Research and Development

• Ongoing phase III trials are investigating belzutifan in combination regimens in the relapsed/refractory, front-line, and adjuvant settings 3.
• Future studies will focus on identifying predictive biomarkers and resistance pathways 3.
• Research is ongoing to optimize therapeutic benefits from belzutifan and to improve the outcome of HIF-2α-driven tumors 4, 5.