FDA Approves Belzutifan for Treatment of Advanced Renal Cell Carcinoma


Belzutifan (Welireg; Merck) demonstrated superior progression-free survival compared to everolimus in advanced renal cell carcinoma.

The FDA has approved belzutifan (Welireg; Merck) for the treatment of adults with advanced renal cell carcinoma (RCC) following programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI), according to a press release from Merck. Belzutifan is an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor.

a close-up of a microscope lens capturing a vibrant blue cancer cell | Image Credit: catalin - stock.adobe.com

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“Despite recent progress in the treatment of advanced RCC, there is yet to be an option specifically approved for patients whose disease progresses following a PD-1 or PD-L1 inhibitor and a TKI therapy,” Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, said in the press release. “This approval of belzutifan introduces a meaningful new treatment option for certain patients, as belzutifan reduced the risk of disease progression or death compared to everolimus.”

The approval is based on results from the LITESPARK-005 trial, specifically designed to evaluate individuals whose disease has progressed following a PD-1 or PD-L1 inhibitor and a VEGF-TKI. The LITESPARK-005 study was an open-label, randomized, active-controlled clinical trial. Investigators included 746 patients from the patient population. The individuals could have received up to 3 prior treatment regiments and needed to have measurable disease per RECIST v1.1. Investigators randomly assigned belzutifan 120 mg or everolimus 10 mg orally once daily to the individuals. The patients were evaluated radiologically at 9 weeks from date of randomization, then ever 8 weeks through week 49, and every 12 weeks after, according to the press release.

About The LITESPARK-005 Trial

Trial Name: A Study of Belzutifan (MK-6482) Versus Everolimus in Participants With Advanced Renal Cell Carcinoma (MK-6482-005)

ClinicalTrials.gov ID: NCT04195750

Sponsor: Merck Sharp & Dohme LLC

Estimated Completion Date: September 2025

The results showed that belzutifan demonstrated superior progression-free survival (PFS) compared to everolimus in advanced RCC, following treatment with a PD1 or PD-L1 inhibitor and VEGF receptor-targeted therapy, given in sequence or combination. Additionally, belzutifan reduced the risk of disease progression or death by 25% compared to everolimus. It also showed an objective response rate of 22% compared to 4% with everolimus, with a complete response (CR) rate of 4% and partial response (PR) of 19% compared to no CR rates and a PR rate of 4%, respectively.

“In 2021, [belzutifan] became the first HIF-2α inhibitor therapy approved in the U.S. for the treatment of adult patients with certain [Von Hippel-Lindau] disease-associated tumors and is now approved for eligible patients with advanced RCC,” Marjorie Green, MD, senior vice president and head of late-stage oncology in global clinical development at Merck Research Laboratories, said in the press release. “This approval of [belzutifan] marks the first new therapeutic class available for eligible patients with advanced RCC in nearly a decade and was based on the statistically significant [PFS] benefit observed in patients following treatment with a PD-1 or PD-L1 inhibitor and a VEGF-TKI when compared to everolimus.”

The median duration of exposure was 7.6 months, ranging from 0.1 to 28.5 months. Serious adverse reactions occurred in 38% of individuals receiving belzutifan and included hypoxia, anemia, pneumonia, hemorrhage, and pleural effusion. The drug’s boxed warning label includes exposure to belzutifan during pregnancy can cause embryo-fetal harm, therefore pregnancy status should be verified prior to initiation of the drug. Further, belzutifan could cause severe anemia, which can require blood transfusion, and can cause severe hypoxia, which can require discontinuation, supplemental oxygen, or hospitalization.


FDA approves Merck’s Welireg (belzutifan) for the treatment of patients with advanced renal cell carcinoma following a PD-1 or PD-L1 inhibitor and a VEGF-TKI. News release. Merck. December 14, 2023. Accessed December 15, 2023. https://www.merck.com/news/fda-approves-mercks-welireg-belzutifan-for-the-treatment-of-patients-with-advanced-renal-cell-carcinoma-rcc-following-a-pd-1-or-pd-l1-inhibitor-and-a-vegf-tki/

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