# Belzutifan

Source: https://onco.cc/drugs/belzutifan/  
OnCo record `belzutifan` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Belzutifan is the first HIF-2α inhibitor, born from Nobel-winning biology, and is now approved after kidney cancer surgery with pembrolizumab.

## Summary

Belzutifan is a small-molecule HIF-2-alpha inhibitor that blocks HIF-2-alpha from dimerising with ARNT, silencing the hypoxia programme that drives clear-cell kidney cancer when VHL is lost; it is taken as 120 mg once daily. It was approved in 2021 for VHL disease-associated renal cell carcinoma, CNS haemangioblastoma and pancreatic neuroendocrine tumours, in 2023 for advanced RCC after PD-1/PD-L1 and VEGF-TKI therapy (LITESPARK-005), in 2025 for pheochromocytoma and paraganglioma, and in Q2 2026 as adjuvant therapy for clear-cell RCC with pembrolizumab (LITESPARK-022). Merck markets it. Anaemia and hypoxia are on-mechanism effects because HIF-2-alpha regulates erythropoietin. Whether the adjuvant benefit translates into survival, and which patients respond, remain open. For a newcomer: the first drug from the Nobel-winning biology of how cells sense oxygen.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-04
- Brand: Welireg
- Modality: Small-molecule HIF-2α inhibitor
- Mechanism: Blocks HIF-2α/ARNT dimerisation.
- Approvals: US 2021: VHL-associated RCC, CNS haemangioblastoma, pNET; US 2023: Advanced RCC after PD-1/PD-L1 and VEGF-TKI; US 2026: Adjuvant clear-cell RCC with pembrolizumab; EU 2025: ccRCC after ≥2 lines; VHL-associated tumours; 12 Feb 2025 (conditional)
- Dosing: Oral; 120 mg once daily

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Belzutifan
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Belzutifan

## Connected records

- cancers: [Clear cell renal cell carcinoma](https://onco.cc/cancers/clear-cell-rcc/), [Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)](https://onco.cc/cancers/hereditary-ppgl/), [Metastatic pheochromocytoma and paraganglioma](https://onco.cc/cancers/metastatic-ppgl/), [Neuroendocrine tumours](https://onco.cc/cancers/neuroendocrine/), [Pancreatic neuroendocrine tumours](https://onco.cc/cancers/pancreatic-net/), [Pheochromocytoma and paraganglioma (PPGL)](https://onco.cc/cancers/pheochromocytoma-paraganglioma/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Spinal cord tumours (intramedullary and intradural)](https://onco.cc/cancers/spinal-cord-tumours/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ARNT](https://onco.cc/targets/arnt/), [HIF-1α (HIF1A)](https://onco.cc/targets/hif1a/), [HIF-2α](https://onco.cc/targets/hif2a/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- trials: [A Study of Belzutifan (MK-6482) in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma (MK-6](https://onco.cc/trials/nct05468697/), [A Study of Belzutifan (MK-6482) in Participants With Advanced Renal Cell Carcinoma (MK-6482-013)](https://onco.cc/trials/nct04489771/), [A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, vs Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)-China Extension Study](https://onco.cc/trials/nct05899049/), [A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003)](https://onco.cc/trials/nct03634540/), [Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL](https://onco.cc/trials/nct04924075/), [Extension Study for Participants in Studies That Include Belzutifan (MK-6482-043/LITESPARK-043)](https://onco.cc/trials/nct07405164/), [LITESPARK-005](https://onco.cc/trials/litespark-005/), [LITESPARK-011](https://onco.cc/trials/nct04586231/), [LITESPARK-012](https://onco.cc/trials/litespark-012/), [LITESPARK-022](https://onco.cc/trials/litespark-022/), [Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Solid Tumors (MK-6482-016)](https://onco.cc/trials/nct04976634/), [Study of Belzutifan (MK-6482) Plus Fulvestrant for ER+/HER2- Metastatic Breast Cancer (MK-6482-029/LITESPARK-029)](https://onco.cc/trials/nct06428396/), [Substudy 03A: A Study of Immune and Targeted Combination Therapies in Participants With First Line (1L) Renal Cell Carcinoma (MK-3475-03A)](https://onco.cc/trials/nct04626479/), [Substudy 03B: A Study of Immune and Targeted Combination Therapies in Participants With Second Line Plus (2L+) Renal Cell Carcinoma (MK-3475-03B/KEYMAKER-U03)](https://onco.cc/trials/nct04626518/), [Substudy 03C: A Study of Combination Therapies in Participants With Renal Cell Carcinoma With Recurrent Disease During or After Anti-PD-(L)1 Therapy (](https://onco.cc/trials/nct07049926/)
- terms: [Angiogenesis](https://onco.cc/terms/angiogenesis/), [MEN1 and hereditary neuroendocrine syndromes](https://onco.cc/terms/men1-hereditary-net/), [SDH deficiency (SDHB immunohistochemistry loss)](https://onco.cc/terms/sdh-deficiency/), [Von Hippel-Lindau disease](https://onco.cc/terms/vhl-disease/)
- ideas: [Biomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)](https://onco.cc/ideas/idea-adjuvant-selection-rcc/)
- pathways: [Choline metabolism in cancer](https://onco.cc/pathways/choline-metabolism-in-cancer/), [Renal cell carcinoma (KEGG map)](https://onco.cc/pathways/renal-cell-carcinoma-signalling/), [Synthetic lethality: paired dependencies](https://onco.cc/pathways/synthetic-lethality-map/), [The angiogenic switch & tumour vessels](https://onco.cc/pathways/angiogenic-switch/), [VEGF angiogenesis](https://onco.cc/pathways/vegf-angiogenesis/), [VHL / HIF oxygen sensing](https://onco.cc/pathways/hif-vhl/)
- people: [Laurence Albiges](https://onco.cc/people/laurence-albiges/), [Toni K. Choueiri](https://onco.cc/people/toni-choueiri/), [William G. Kaelin Jr.](https://onco.cc/people/william-kaelin/)
- key papers: [Belzutifan for renal cell carcinoma and other tumours in von Hippel-Lindau disease](https://onco.cc/key-papers/paper-belzutifan-vhl-jonasch-nejm-2021/), [Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial](https://onco.cc/key-papers/paper-litespark-011-motzer-lancet-2026/)
- institutions: [Harold C. Simmons Comprehensive Cancer Center, UT Southwestern](https://onco.cc/institutions/utsw-simmons/)

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