FDA Launches Priority Review of Belzutifan for Previously Treated Advanced RCC


The FDA has granted belzutifan priority review designation based on data from the phase 3 LITESPARK-005 trial.

FDA Launches Priority Review of Belzutifan for Previously Treated Advanced RCC

FDA Launches Priority Review of Belzutifan for Previously Treated Advanced RCC

The FDA has granted priority review to the supplemental new drug application (sNDA) for belzutifan (Welireg). The sNDA seeks approval for the indication of patients with previously treated advanced renal cell carcinoma (RCC) following immune checkpoint and anti-angiogenic therapies.1

The sNDA is supported by data from a prespecified interim analysis of the phase 3 LITESPARK-005 trial (NCT04195750), which showed that treatment with belzutifan led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with everolimus (Afinitor), per an independent data monitoring committee. Additionally, patients treated with belzutifan experienced a statistically significant improvement in objective response rate (ORR). Full data will be presented at an upcoming medical meeting.2

The target action date under the Prescription Drug User Fee Act is January 17, 2024.1

“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, Global Clinical Development, at Merck Research Laboratories, stated in a news release. “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 [belzutifan] to these patients as quickly as possible.”

Previously, in August 2021, the FDA approved belzutifan for the treatment of adult patients with von Hippel-Lindau disease who require therapy for associated RCC, central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors that do not require immediate surgery.3

LITESPARK-005 was a randomized, open-label study that enrolled patients at least 18 years of age with unresectable, locally advanced, or metastatic clear cell RCC who experienced disease progression on or after systemic treatment for locally advanced or metastatic RCC with both a PD-1/PD-L1 checkpoint inhibitor and a VEGF TKI, either in sequence or in combination.4 No more than 3 prior systemic regimens for locally advanced or metastatic RCC were allowed.

Key exclusion criteria included known CNS metastases and/or carcinomatous meningitis; clinically significant cardiac disease; poorly controlled hypertension; and moderate to severe hepatic impairment.

The trial enrolled 746 patients who were randomly assigned to receive 120 mg of oral belzutifan once per day or 10 mg of oral everolimus once per day.1

PFS and overall survival (OS) served as the co-primary end points. ORR, duration of response, and safety were key secondary end points.

Findings from the prespecified interim analysis demonstrated a trend toward improvement in OS with belzutifan; however, these data did not reach statistical significance. OS will be tested again at a subsequent analysis.2

Regarding safety, findings for belzutifan were consistent with data from previously reported studies.


  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 19, 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. Merck announces WELIREG (belzutifan) phase 3 LITESPARK-005 trial met primary endpoint of progression-free survival in certain previously treated patients with advanced renal cell carcinoma. News release. Merck. August 18, 2023. Accessed September 19, 2023. https://www.merck.com/news/merck-announces-welireg-belzutifan-phase-3-litespark-005-trial-met-primary-endpoint-of-progression-free-survival-in-certain-previously-treated-patients-with-advanced-renal-cell-carcinoma/
  3. FDA approves belzutifan for cancers associated with von Hippel-Lindau disease. News release. FDA. August 13, 2021. Accessed August 18, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-cancers-associated-von-hippel-lindau-disease
  4. A study of belzutifan (MK-6482) versus everolimus in participants with advanced renal cell carcinoma (MK-6482-005). ClinicalTrials.gov. Updated August 1, 2022. Accessed September 19, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04195750
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