FDA

Welireg approved for pheochromocytoma or paraganglioma

May 16, 2025

FDA approved Welireg (belzutifan), an inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α), for the treatment of adult and pediatric patients ≥12 years of age with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL).

Welireg was previously approved for for the treatment of von Hippel-Lindau disease and advanced renal cell carcinoma.

Efficacy

Efficacy was evaluated in the open-label, multi-cohort LITESPARK-015 trial (NCT04924075). Cohort A1 was conducted in 72 patients with locally advanced or metastatic PPGL not amenable to surgery or curative treatment. Patients with concomitant hypertension with adequately controlled BP were required to have no change in antihypertensive meds for at least 2 weeks prior to study initiation. Patients with carcinomatous meningitis were excluded.

The major efficacy outcome measure was objective response rate (ORR). Additional efficacy outcome measures were duration of response (DOR) and the number of patients who had a reduction in ≥1 antihypertensive medication by ≥50% maintained for ≥6 months. ORR was 26% (95% confidence interval [CI], 17, 38). Median DOR was 20.4 months (95% CI, 8.3, NR). Of the 60 patients on baseline antihypertensive medications, 19 (32% [95% CI, 20, 45]) had a reduction in ≥1 antihypertensive medication by ≥50% for ≥6 months.

Safety

The most common adverse reactions (≥25%), including lab abnormalities, were anemia, fatigue, musculoskeletal pain, decreased lymphocytes, increased ALT, increased AST, increased calcium, dyspnea, increased potassium, decreased leukocytes, headache, increased alkaline phosphatase, dizziness, and nausea.

Recommended dose

The recommended belzutifan dosage for adults is 120 mg PO once daily. The recommended dosage for pediatric patients ≥12 years of age is based on body weight. For pediatric patients weighing ≥40 kg, the dose is 120 mg PO once daily. For those weighing <40 kg, the dose is 80 mg PO once daily. Continue belzutifan until disease progression or unacceptable toxicity.

Sources:

FDA approves belzutifan for pheochromocytoma or paraganglioma. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-pheochromocytoma-or-paraganglioma

FDA Approves Merck’s WELIREG® (belzutifan) for the Treatment of Adults and Pediatric Patients 12 Years and Older With Locally Advanced, Unresectable, or Metastatic Pheochromocytoma or Paraganglioma (PPGL). [News release]. 2025. https://www.merck.com/news/fda-approves-mercks-welireg-belzutifan-for-the-treatment-of-adults-and-pediatric-patients-12-years-and-older-with-locally-advanced-unresectable-or-metastatic-pheochromocytoma-or-par/

Welireg (belzutifan). [package insert]. Merck. https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_pi.pdf Revised May 2025. Accessed May 15, 2025.