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Welireg Now FDA Approved for Patients with Advanced Renal Cell Carcinoma

Web Exclusives - FDA Approvals

On December 14, 2023, the FDA approved a new indication for belzutifan (Welireg; Merck), a hypoxia-inducible factor inhibitor, for the treatment of advanced renal cell carcinoma (RCC) in adults who have received a PD-1 or PD-L1 inhibitor and a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI). The FDA granted this approval priority review.

Belzutifan is the first hypoxia-inducible factor-2 alpha inhibitor approved for the treatment of this adult population with advanced RCC.

Belzutifan was previously approved for adults with von Hippel-Lindau disease who require treatment for 1 of 3 associated tumor types, including RCC, central nervous system hemangioblastomas, and pancreatic neuroendocrine tumors, not requiring immediate surgery.

This current FDA approval was based on the results of the phase 3 LITESPARK-005 (NCT04195750) study, an open-label, randomized, head-to-head clinical trial that evaluated the efficacy of belzutifan in unresectable, locally advanced or metastatic clear-cell RCC that progressed after the patient received a PD-1 or PD-L1 checkpoint inhibitor and a VEGF TKI. The 746 patients in the trial were randomized 1:1 to treatment with belzutifan 120 mg or everolimus 10 mg once daily. The trial stratified randomization by the number of previous VEGF TKIs and International Metastatic RCC Database Consortium risk category.

The main efficacy measures were progression-free survival (PFS) and overall survival (OS).

Treatment with belzutifan resulted in a significant improvement in PFS compared with everolimus (hazard ratio, 0.75; 95% confidence interval [CI], 0.63-0.90; 1-sided P=.0008). Kaplan-Meier curves displayed nonproportional hazards with similar median PFS estimates of 5.6 months (95% CI, 3.9-7.0) for belzutifan and 5.6 months (95% CI, 4.8-5.8) for everolimus.

The OS results were immature at the time of the current analysis, with 59% of deaths reported, but there was no trend toward a detriment for belzutifan versus everolimus. Improved tolerability for belzutifan compared with everolimus was supported by a descriptive analysis of patient-reported symptoms and functional outcomes.

The most common (≥25%) adverse events with belzutifan were decreased hemoglobin, fatigue, musculoskeletal pain, increased creatinine, decreased lymphocytes, increased alanine aminotransferase, decreased sodium, increased potassium, and increased aspartate aminotransferase.

“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,” said Toni K. Choueiri, MD, LITESPARK-005 Study Chair and Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, in a 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,” he added.

The recommended dose of belzutifan is 120 mg orally, once daily, until disease progression or unacceptable adverse events.

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Last modified: January 22, 2024