First Oral Therapy for Pheochromocytoma and Paraganglioma  

The FDA has approved belzutifan for certain patients with pheochromocytoma and paraganglioma. 

The U.S. Food and Drug Administration (FDA) has approved belzutifan (Welireg) for the treatment of patients 12 years and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL). 

Belzutifan is a targeted therapy that inhibits the HIF pathway that becomes activated in low oxygen conditions, which frequently occur within tumors. It is the first oral therapy to receive FDA approval for PPGL.  

PPGL develops from cells in and around the adrenal gland (shown here in yellow), which produces hormones that can raise blood pressure. The adrenal glands are found on top of the kidneys (shown here in red). 

PPGL can cause high blood pressure. Consequently, standard treatment for PPGL can involve medications to control this hypertension, in addition to surgery, radiation, and chemotherapy to treat the cancer. 

The approval is based on results from the open-label phase II LITESPARK-015 trial, in which 72 patients with locally advanced or metastatic PPGL not amenable to surgery or curative treatment received belzutifan.  

Twenty-six percent (19/72) of patients experienced tumor responses to belzutifan, with half of responses lasting at least 20.4 months. Among the 60 patients who were taking antihypertensive medications, 32% (19/60) were able to reduce medication for high blood pressure for at least six months. 

The recommended adult dose for belzutifan is 120 mg orally once daily. The recommended pediatric dose for belzutifan is 120 mg orally once daily for patients weighing 40 kg or more, and 80 mg orally once daily for patients weighing less than 40 kg. Belzutifan is given until disease progression or unacceptable toxicity. 

Pheochromocytoma and paraganglioma—PPGL—are rare neuroendocrine tumors that arise from specialized cells called chromaffin cells, which produce the hormones that increase blood pressure. Pheochromocytomas develop in the center of the adrenal gland, and paragangliomas develop near certain blood vessels and nerves outside the adrenal gland. It has been estimated that pheochromocytoma and paraganglioma affect approximately eight and two people out of every 1 million, respectively. 

The FDA rendered its decision on May 14, 2025. Check this resource for updated information on all therapeutics regulated by the FDA.