Belzutifan is approved by the USFDA for pheochromocytoma or paraganglioma

On May 14, 2025, the Food and Drug Administration sanctioned belzutifan (Welireg, Merck & Co., Inc.) for adult and pediatric patients aged 12 and older diagnosed with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL). This is the inaugural FDA approval of an oral treatment for PPGL.

The efficacy was assessed in LITESPARK-015 (NCT04924075), an open-label, multi-cohort study. Cohort A1 comprised 72 patients with detectable disease confirmed by blinded independent central review (BICR) according to RECIST v1.1, established histological diagnosis of PPGL, and locally progressed or metastatic disease unsuitable for surgical or curative intervention. Patients with concurrent hypertension and appropriately controlled blood pressure were required to maintain a stable regimen of antihypertensive drugs for a minimum of 2 weeks before the commencement of the research. Patients diagnosed with carcinomatous meningitis were excluded.

The primary efficacy outcome measure was the objective response rate (ORR) assessed by blinded independent central review (BICR) according to RECIST version 1.1. The supplementary efficacy outcome measures included the duration of response (DOR) and the count of patients who achieved a decrease of at least 50% in one antihypertensive medication, sustained for a minimum of six months.

The overall response rate (ORR) was 26% (95% confidence interval: 17, 38). The median duration of response (DOR) was 20.4 months (95% confidence interval: 8.3, not reached). Among the 60 patients receiving baseline antihypertensive drugs, 19 (32% [95% CI: 20, 45]) experienced a reduction of at least 50% in at least one antihypertensive medication for a minimum duration of six months.

The predominant adverse reactions (≥25%), encompassing laboratory abnormalities, included anemia, fatigue, musculoskeletal pain, reduced lymphocytes, elevated alanine aminotransferase, elevated aspartate aminotransferase, increased calcium, dyspnea, elevated potassium, decreased leukocytes, headache, elevated alkaline phosphatase, dizziness, and nausea.

The advised dosage of belzutifan for adults is 120 mg taken orally once per day. The advised dosage for pediatric patients aged 12 years and older is determined by body weight. For pediatric patients weighing 40 kg or more, the dosage is 120 mg administered orally once daily. For pediatric patients weighing less than 40 kg, the dosage is 80 mg administered orally once a day. Administer belzutifan until disease progression or intolerable toxicity occurs.