The supplemental new drug application is supported by findings from the LITESPARK-005 trial.
The FDA has granted a priority review designation to a supplemental new drug application (sNDA) for belzutifan (Welireg) for the treatment of patients with metastatic renal cell carcinoma (RCC) whose disease has progressed following prior treatment with a PD-1/L1 inhibitor and a VEGF-TKI.1
The sNDA is supported by findings from the LITESPARK-005 trial (NCT04195750),2 which showed that belzutifan significantly reduced the risk of disease progression or death vs everolimus (Afinitor) in patients with metastatic RCC.
Merck (MSD), the developer of the HIF-2α inhibitor, previously reported that belzutifan demonstrated a significant improvement in the study’s co-primary end point of progression-free survival compared to everolimus, as determined through a pre-specified interim analysis conducted by an independent Data Monitoring Committee. The company also noted a trend toward improvement in overall survival with belzutifan, the trial’s other co-primary end point, although the difference between belzutifan and everolimus did not reach statistical significance.3
“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. 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,” said Marjorie Green, MD, in a news release.1 Green is the senior vice president and head of late-stage oncology in global clinical development at Merck Research Laboratories.
Currently, belzutifan is approved in the United States for patients with von Hippel-Lindau disease who require therapy for associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors that do not require immediate surgery.
The FDA is scheduled to decide on the sNDA on or before January 17, 2024.
The LITESPARK-005 trial2 was a randomized, open-label phase 3 trial that enrolled 746 adult patients with metastatic RCC. Participants were randomly assigned 1:1 to receive 120 mg of belzutifan orally once daily or 10 mg of everolimus orally once daily.
Patients were included in the study if they had received no more than 3 prior systemic treatment regimens for RCC; had adequate organ function; if male, were abstinent from heterosexual intercourse or agreed to use contraception during the study period; and, if female, were not pregnant, breastfeeding, or either did not have the potential to become pregnant or agreed to wear contraceptives during the study period.
Secondary end points for LITESPARK-005 include objective response rate (ORR), duration of response, and safety/tolerability. The interim analysis of the trial data3 showed a statistically significant improvement in ORR with belzutifan compared with everolimus, according to Merck. No new safety signals with either treatment were reported.
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. Published online and 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. National Institutes of Health US National Library of Medicine ClinicalTrials.gov. A study of belzutifan (MK-6482) versus everolimus in participants with advanced renal cell carcinoma (MK-6482-005). Last updated August 1, 2022. Accessed September 19, 2023. https://clinicaltrials.gov/study/NCT04195750
3. Merck announces WELIRIG (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.businesswire.com/news/home/20230818906049/en/Merck-Announces-WELIREG%C2%AE-belzutifan-Phase-3-LITESPARK-005-Trial-Met-Primary-Endpoint-of-Progression-Free-Survival-in-Certain-Previously-Treated-Patients-With-Advanced-Renal-Cell-Carcinoma