By Fineline Cube 
The US Food and Drug Administration (FDA) announced this week an indication extension approval for Merck, Sharp & Dohme’s (MSD; NYSE: MRK) oral drug Welireg (belzutifan). The approval expands its use to treat adult and pediatric patients aged 12 years and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL).
Drug Profile and Previous Approvals
Welireg, a HIF-2α inhibitor, is already registered in the US for treating adult patients with von Hippel-Lindau (VHL) disease requiring therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET). It is also indicated for advanced RCC previously treated with a PD-1/PD-L1 inhibitor and a VEGF-TKI.
PPGL and Clinical Trial Data
PPGL, a rare tumor originating from the same tissue, may arise due to specific genetic syndromes or mutations. Pheochromocytomas develop in the adrenal gland, while paragangliomas form in extra-adrenal tissue. The approval is supported by data from the single-arm Phase II LITESPARK-015 study, which demonstrated that a daily dose of 120 mg of belzutifan achieved the primary endpoint of objective response rate (ORR).
Safety Information
The Welireg label includes a boxed warning about the risk of embryo-fetal harm if exposure occurs during pregnancy. Healthcare providers should verify pregnancy status before starting treatment and advise patients on the risks and the necessity of effective non-hormonal contraception. Additionally, Welireg can cause severe anemia potentially requiring blood transfusion and severe hypoxia that may necessitate discontinuation, supplemental oxygen, or hospitalization. Regular monitoring for these conditions is essential.-Fineline Info & Tech