FDA Okays Belzutifan for Pheochromocytoma or Paraganglioma

Medscape

15-05-2025

The US Food and Drug Administration (FDA) has approved belzutifan (Welireg, Merck) for adult and pediatric patients aged 12 years or older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL).
It is the first US approval of 'an oral therapy for PPGL,' the FDA said in a press release.
The hypoxia-inducible factor 2 alpha inhibitor was previously approved for von Hippel-Lindau disease and advanced renal cell carcinoma.
PPGLs are rare and related neuroendocrine tumors that can secrete catecholamines. Pheochromocytoma develops in the adrenal glands, while paraganglioma can develop in various other places. The tumors can lead to life-threatening hypertensive crises.
Approval was based on the open-label, multicohort LITESPARK-015 trial with 72 patients having PPGL tumors not amenable to surgery or curative treatment.
The objective response rate was 26%; median duration of response was 20.4 months (95% CI, 8.3, NR). Of the 60 patients on baseline antihypertensive medications, 19 (32%) had a reduction in at least one antihypertensive medication by at least 50% for at least 6 months.
The most common adverse reactions in 25% or more of subjects included anemia, fatigue, musculoskeletal pain, decreased lymphocytes, increased alanine aminotransferase, increased aspartate aminotransferase, increased calcium, dyspnea, increased potassium, decreased leukocytes, headache, increased alkaline phosphatase, dizziness, and nausea.
Labelling carries a black box warning of embryo-fetal toxicity.
The recommended dose for adults is 120 mg oral belzutifan, taken once daily. The recommended dose for pediatric patients aged 12 years and older is based on body weight. For those with a body weight of 40 kg or more, the dose is 120 mg oral belzutifan, taken once daily. For pediatric patients under 40 kg, the dose is 80 mg oral belzutifan, taken once daily.
Treatment continues until disease progression or unacceptable toxicity.
Ninety 40 mg tablets cost $32,624.23, according to drugs.com.