FDA Grants Priority Review to New Drug Application for Belzutifan for Advanced Renal Cell Carcinoma


The sNDA is based on data that evaluated belzutifan (Welireg; Merck) compared to everolimus (Afinitor; Novartis) for the treatment of advanced renal cell carcinoma.

The FDA has accepted and granted priority review to a new supplemental new drug application (sNDA) seeking approval for belzutifan (Welireg; Merck) for the treatment of adults with advanced renal cell carcinoma (RCC) after immune checkpoint and anti-angiogenic therapies.1

Belzutifan is an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor. The sNDA is based on data from the LITESPARK-005 trial (NCT04195750), a randomized, open-label phase 3 trial that evaluated belzutifan compared to everolimus (Afinitor; Novartis) for the treatment of advanced RCC that has progressed after prior treatment with PD-1/L1 and vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) therapies, either in sequence or in combination.1

“Patients with advanced RCC whose cancer progresses following immune checkpoint and anti-angiogenic therapies face a poorer prognosis, and for those patients, there is a crucial unmet need for new options with an alternative mechanism of action,” Marjorie Green, MD, senior vice president and head of late-stage oncology in global clinical development of Merck Research Laboratories, said in a statement. “The FDA’s priority review designation of this application reinforces the urgency to provide new options to previously treated patients with advanced RCC, and we are committed to working closely with the FDA to bring Welireg to these patients as quickly as possible.”1

In the study, belzutifan demonstrated clinically meaningful improvements in progression-free survival (PFS).Additionally, investigators observed statistically significant improvements in objective response rate (ORR).2

Furthermore, the safety profile of belzutifan was consistent with what was observed in other studies.2 The most common adverse reactions included decreased hemoglobin, anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea.1

The study included 746 individuals who were enrolled in the study and randomized to receive belzutifan, at 120 mg orally once daily, or everolimus, at 10 mg orally once daily. There were dual primary endpoints of PFS and overall survival, with the secondary endpoints of ORR, duration of response, safety, and tolerability.2

The FDA has a Prescription Drug User Fee Act date of January 17, 2024. Belzutifan was the first HIF-2α therapy that was approved in the United States and is currently approved for the treatment of adults with von Hippel-Lindau who require therapy for associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors and do not require immediate surgery.1

LITESPARK-005 is part of a comprehensive development program for belzutifan, which is comprised of 4 phase 3 trials in RCC. The trials included LITESPARK-011 (NCT04586231) and LITESPARK-012 (NCT04736706), which evaluated belzutifan in the second-line and treatment-naïve advanced disease settings, and LITESPARK-022 (NCT05239728), which evaluated belzutifan in the adjuvant setting.1,2

The rate of incidence of RCC has increased, becoming the ninth most common cancer in the United States, according to a study published in the World Journal of Oncology. Although RCC accounts for 2% of global cancer diagnoses and deaths, it has more than doubled, according to the investigators.3


  1. FDA accepts for priority review Merck’s supplemental new drug application for Welireg (belzutifan) in certain previously treated patients with advanced renal cell carcinoma (RCC). News release. Merck. September 19, 2023. Accessed September 20, 2023. https://www.merck.com/news/fda-accepts-for-priority-review-mercks-supplemental-new-drug-application-for-welireg-belzutifan-in-certain-previously-treated-patients-with-advanced-renal-cell-carcinoma-rcc/
  2. Gallagher A. Study: belzutifan demonstrates improvement in progression-free survival for advanced renal cell carcinoma. Pharmacy Times. August 24, 2023. Accessed September 20, 2023. https://www.pharmacytimes.com/view/study-belzutifan-demonstrates-improvement-in-progression-free-survival-for-advanced-renal-cell-carcinoma
  3. Padala SA, Barsouk A, Thandra KC, Saginala K, et al. Epidemiology of renal cell carcinoma. World J Oncol. 2020;11(3):79-87. doi:10.14740/wjon1279
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