Dr Perez on the FDA Approval of Belzutifan for Advanced Pheochromocytoma and Paraganglioma

“The fact that we now have an FDA approved drug option that was prospectively evaluated in a very strong clinical trial is great, and I think it will mean a lot to patients and providers of this patient population.”

Kimberly Perez, MD, a medical oncologist and co-director of clinical research in the Division of Gastrointestinal Oncology at Dana-Farber Cancer Institute; as well as an assistant professor of medicine at Harvard Medical School, discussed the clinical implications of the FDA approval of belzutifan (Welireg) for the treatment of adult and pediatric patients 12 years of age and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma.

On May 14, 2025, the FDA approved belzutifan for this indication based on data from the phase 2 LITESPARK-015 trial (NCT04924075), which evaluated the agent in patients with advanced disease. In cohort A1 (n = 72), the agent demonstrated a confirmed overall response rate of 26% (95% CI, 17%-38%) and a median duration of response of 20.4 months (95% CI, 8.3-not reached).

Perez emphasized that prior to this approval, systemic treatment options for pheochromocytoma and paraganglioma were limited. The only previously approved agent, iobenguane I 131 (Azedra), is no longer commercially available, she stated. Alternative therapies—including TKIs and cytotoxic chemotherapy—have been used in this population but are associated with notable toxicity concerns, particularly in patients with catecholamine-secreting tumors where hypertension is a dominant clinical feature, according to Perez.

Belzutifan, a selective HIF-2α inhibitor, uses a novel mechanism of action compared with historically used regimens. Perez noted that the absence of exacerbated hypertensive events associated with belzutifan is clinically meaningful given the underlying biology of these tumors and their association with catecholamine excess.

Belzutifan was generally well tolerated in LITESPARK-015, with the most frequently reported adverse effects—occurring in at least 25% of patients—consisting of anemia; fatigue; musculoskeletal pain; decreased lymphocyte and leukocyte counts; elevated alanine aminotransferase, aspartate aminotransferase, calcium, potassium, and alkaline phosphatase levels; dyspnea; dizziness; headache; and nausea.

The recommended dosage of belzutifan is 120 mg once daily for adult patients and pediatric patients weighing at least 40 kg. For pediatric patients weighing under 40 kg, the recommended dose is 80 mg once daily. Treatment should continue until disease progression or the development of unacceptable toxicity.