On December 14, 2023, the U.S. Food and Drug Administration (FDA) approved belzutifan (Welireg™) for patients with advanced renal cell carcinoma (RCC) following treatment with a 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).

FDA update

Efficacy was evaluated in LITESPARK-005 (NCT04195750), an open-label, randomized, head-to-head trial of 746 patients with unresectable locally advanced or metastatic clear cell RCC that had progressed following both a PD-1 or PD-L1 checkpoint inhibitor and a VEGF-TKI. Patients were randomized 1:1 (stratified by International Metastatic RCC Database Consortium risk category and number of prior VEGF-TKIs) to receive 120 mg belzutifan or 10 mg everolimus once daily.

The major efficacy outcome measures were progression- free survival (PFS), assessed by blinded independent central review, and overall survival (OS). Compared with everolimus, patients treated with belzutifan demonstrated a statistically significant improvement in PFS (HR = 0.75; 95% CI = 0.63, 0.90; p = 0.0008]. Kaplan-Meier curves estimated a median PFS of 5.6 months (95% CI = 3.9, 7.0) in the belzutifan arm and 5.6 months (95% CI: 4.8, 5.8) for those receiving everolimus. OS results were immature at the current analysis with 59% of deaths reported, researchers did not observe a trend toward detriment. A descriptive analysis of patient-reported symptom and functional outcomes was supportive of improved tolerability for belzutifan compared to everolimus.

The most common adverse reactions reported in at least 25% of patients receiving belzutifan were decreased hemoglobin, fatigue, musculoskeletal pain, increased creatinine, decreased lymphocytes, increased alanine aminotransferase, decreased sodium, increased potassium, and increased aspartate aminotransferase.

The recommended belzutifan dose is 120 mg orally once daily until patients experience disease progression or unacceptable toxicity.

View the full prescribing information for belzutifan.

The applicant voluntarily submitted belzutifan’s review with Assessment Aid to facilitate FDA’s assessment. The application was also granted priority review. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Office of Oncology Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.