Mechanism of Action for WELIREG™ (belzutifan)
WELIREG works differently by targeting HIF-2α, a key driver of tumor growth1–3
WELIREG is indicated for the treatment of adult patients with advanced RCC following an anti–PD-1/L1 and
a VEGF-TKI.
The approval of WELIREG marks the first treatment option in a novel therapeutic class available for your appropriate patients with advanced RCC since 2015.3
HIF-1β = hypoxia-inducible factor 1 beta; HIF-2α = hypoxia-inducible factor 2 alpha; PD-1 = programmed death receptor-1; PD-L1 = programmed death-ligand 1; RCC = renal cell carcinoma; VEGF-TKI = vascular endothelial growth factor tyrosine kinase inhibitor; VHL = von Hippel-Lindau.


References: 1. Targeted drug therapy for kidney care. American Cancer Society. Last revised December 18, 2023. Accessed March 22, 2024. https://www.cancer.org/cancer/kidney-cancer/treating/targeted-therapy.html. 2. Shenoy N, Pagliaro L. Sequential pathogenesis of metastatic VHL mutant clear cell renal cell carcinoma: putting it together with a translational perspective. Ann Oncol. 2016;27(9):1685–1695. 3. Yap NY, Khoo WT, Perumal K, et al. Practical updates in medical therapy for advanced and metastatic renal cell carcinoma. Urol Sci. 2018;29(3):120–128. 4. Correa AF, Rini BI, Linehan WM, Schmidt LS, Lane BR, Uzzo RG. Cancer of the kidney. In: DeVita VT Jr, Lawrence TS, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 12th ed. Wolters Kluwer; 2022:729–755. 5. Kaelin WG Jr. HIF2 inhibitor joins the kidney cancer armamentarium. J Clin Oncol. 2018;36(9):908–910. 6. Kaelin WG Jr. The VHL tumor suppressor gene: insights into oxygen sensing and cancer. Trans Am Clin Climatol Assoc. 2017;128:298–307. 7. Choi WSW, Boland J, Lin J. Hypoxia-inducible factor-2α as a novel target in renal cell carcinoma. J Kidney Cancer VHL. 2021;8(2):1–7. 8. Mattila KE, Vainio P, Jaakkola PM. Prognostic factors for localized clear cell renal cell carcinoma and their application in adjuvant therapy. Cancers. 2022;14(1):239.