Belzutifan Approved for Adult and Pediatric Patients With Pheochromocytoma or Paraganglioma
On May 14, 2025, the US Food and Drug Administration approved belzutifan for the treatment of adult and pediatric patients 12 years and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL). This approval, representing the first for an oral therapy for PPGL, was based on results from the LITESPARK-015 trial.
Cohort A1 of the open-label, multi-cohort, phase 2 LITESPARK-015 trial enrolled 72 patients with measurable disease and documented histopathological PPGL diagnosis, and locally advanced or metastatic disease that was not amenable to surgery or curative treatment. While patients with concomitant hypertension were accepted, they had to have adequately controlled blood pressure and must have no change in antihypertensive medications for at least 2 weeks prior to study initiation.
The major efficacy outcome of this trial was objective response rate by blinded independent central review (BICR), with additionally end points including duration of response, and the number of patients with a reduction in at least 1 antihypertensive medication by at least 50% maintained for ≥ 6 months.
The objective response rate by BICR was 26% and the median duration of response was 20.4 months. Of 60 patients with antihypertensive medications at baseline, 19 (32%) had a reduction in at least 1 antihypertensive medication by at least 50% for at least 6 months. The most common adverse events occurring in ≥ 25% of patients and including laboratory abnormalities were 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.
The recommended belzutifan dose for adults is 120 mg administered orally once daily. The recommended belzutifan dose for pediatric patients ≥12 years is 120 mg orally once daily for patients weighing ≥ 40 kg, and 80 mg for patients weighing < 40 kg. Belzutifan should be continued until disease progression or unacceptable toxicity.
Source:
FDA approves belzutifan for pheochromocytoma or paraganglioma. Accessed May 14, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-pheochromocytoma-or-paraganglioma
