Merck announced that the FDA approved WELIREG, an oral inhibitor of hypoxia-inducible factor-2 alpha (HIF-2α), for treating adult patients with advanced renal cell carcinoma (RCC) who have undergone 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).
The approval is grounded in the statistically significant and clinically meaningful outcomes from the LITESPARK-005 trial, the only study in advanced RCC specifically assessing patients who progressed after PD-1 or PD-L1 inhibitor and VEGF-TKI treatment. In this trial, WELIREG demonstrated superior progression-free survival (PFS) with an HR of 0.75 (95% CI, 0.63-0.90; p=0.0008) compared to everolimus in advanced RCC following sequential or combination treatment with a PD-1 or PD-L1 checkpoint inhibitor and a VEGF receptor targeted therapy. WELIREG also exhibited an objective response rate (ORR) of 22% (n=82) (95% CI, 18-27) compared to everolimus's 4% (n=13) (95% CI, 2-6).
The WELIREG label includes a boxed warning highlighting potential embryo-fetal harm with WELIREG exposure during pregnancy. Pregnancy status should be confirmed before initiating WELIREG, and patients should be informed of these risks, emphasizing the need for effective non-hormonal contraception. WELIREG may render some hormonal contraceptives ineffective. Additionally, WELIREG can cause severe anemia requiring blood transfusion, and anemia should be monitored before initiating and periodically during WELIREG treatment. Severe hypoxia, necessitating discontinuation, supplemental oxygen, or hospitalization, is also a potential side effect of WELIREG.