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WELIREGTM (belzutifan) is a selective inhibitor of HIF-2α, a transcription factor that drives tumor growth in advanced RCC1

Mechanism of Action for WELIREG™ (belzutifan): WELIREG Binds to HIF-2α, Which Blocks Interaction With HIF-1β and May Reduce Downstream Activities of Cellular Proliferation, Angiogenesis, and Tumor Growth

[The approval of WELIREG marks the first treatment option in a novel therapeutic class available for your appropriate patients with advanced RCC since [2015].]2

HIF-2α is a transcription factor and one of the key drivers of tumor growth in advanced clear cell RCC3⁠—5

Up to 92% of tumors from patients with any clear cell RCC are characterized by a somatic VHL gene mutation.1,3⁠—5,a Approximately one third of clear cell RCC may progress to advanced disease.6

aWELIREG is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) following immune checkpoint and anti-angiogenic therapies.

Anti–PD-1/L1 = anti–PD-1 or anti–PD-L1; 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.

References:
1. Kaelin WG Jr. The VHL tumor suppressor gene: insights into oxygen sensing and cancer. Trans Am Clin Climatol Assoc. 2017;128:298–307. 2. 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. 3. Correa AF, Rini BI, Linehan WM, et al. 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. 4. Kaelin WG Jr. HIF2 inhibitor joins the kidney cancer armamentarium. J Clin Oncol. 2018;36(9):908–910. 5. 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. 6. Mattila KE, Vainio P, Jaakkola PM. Prognostic Factors for Localized Clear Cell Renal Cell Carcinoma and Their Application in Adjuvant Therapy. Cancers (Basel). 2022;14(1):239.

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