On 14 December 2023, the US Food and Drug Administration (FDA) approved belzutifan (Welireg, Merck & Co., Inc.) for patients with advanced renal cell carcinoma (RCC) following a programmed death receptor 1 (PD1) or programmed death-ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI).<\/p>\n
Efficacy was evaluated in LITESPARK-005 (NCT04195750), an open-label, randomised, head-to-head study of 746 patients with unresectable locally advanced or metastatic clear cell RCC that had progressed following both a PD1 or PD-L1 checkpoint inhibitor and a VEGF TKI. Patients were randomised 1:1 to receive 120 mg belzutifan or 10 mg everolimus once daily. Randomisation was stratified by International Metastatic RCC Database Consortium risk category and number of prior VEGF TKIs.<\/p>\n
The major efficacy outcome measures were progression-free survival (PFS) assessed by blinded independent central review and overall survival (OS).<\/p>\n
A statistically significant improvement in PFS was demonstrated for belzutifan compared with everolimus, with a hazard ratio of 0.75 (95% confidence interval [CI] 0.63, 0.90; 1-sided p-value = 0.0008). Kaplan-Meier curves reflected non-proportional hazards with similar median PFS estimates 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. While OS results were immature at the current analysis, with 59% of deaths reported, no trend towards a detriment was observed. A descriptive analysis of patient-reported symptom and functional outcomes was supportive of improved tolerability for belzutifan compared to everolimus.<\/p>\n
The most common adverse reactions (\u226525% incidence) in patients receiving belzutifan were decreased haemoglobin, fatigue, musculoskeletal pain, increased creatinine, decreased lymphocytes, increased alanine aminotransferase, decreased sodium, increased potassium, and increased aspartate aminotransferase.<\/p>\n
The recommended belzutifan dose is 120 mg administered orally once daily until disease progression or unacceptable toxicity.<\/p>\n
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA\u2019s assessment.<\/p>\n
This application was granted priority review.<\/p>\n
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System.<\/p>\n
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA\u2019s Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n