The U.S. Food and Drug Administration approved belzutifan (Welireg, Merck & Co., Inc.) for use in adult and pediatric patients aged 12 years and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma. It is the first oral therapy approved for this indication.

Efficacy was demonstrated in the open-label, multicohort LITESPARK-015 trial (NCT04924075). Cohort A1 enrolled 72 patients with histologically confirmed, measurable pheochromocytoma or paraganglioma (PPGL) that was not amenable to surgery or curative treatment. Patients with adequately controlled hypertension were required to maintain stable antihypertensive regimens for at least 2 weeks prior to enrollment. Those with carcinomatous meningitis were excluded.

The primary efficacy endpoint was objective response rate (ORR) assessed by blinded independent central review using RECIST v1.1. Secondary endpoints included duration of response (DOR) and reduction in antihypertensive medication. The ORR was 26%, with a median DOR of 20.4 months. Among 60 patients who received antihypertensive therapy at baseline, 19 (32%) achieved a reduction of at least 50% in one antihypertensive medication that was sustained for 6 months or more.

The most common adverse reactions (at least 25%), including laboratory abnormalities, were anemia, fatigue, musculoskeletal pain, lymphopenia, increased alanine aminotransferase, increased aspartate aminotransferase, hypercalcemia, dyspnea, hyperkalemia, leukopenia, headache, increased alkaline phosphatase, dizziness, and nausea.

The recommended adult dose is 120 mg orally once daily. In pediatric patients 12 years and older, dosing is based on body weight: 120 mg daily for those who weigh at least 40 kg and 80 mg daily for those who weigh less than 40 kg. Treatment should continue until disease progression or unacceptable toxicity are reached.

The application received priority review and used the Assessment Aid to facilitate regulatory evaluation. Belzutifan was reviewed under the U.S. Food and Drug Administration's (FDA) expedited programs for serious conditions. Clinicians should report serious adverse events to the FDA MedWatch system. For single-patient investigational new drug inquiries related to investigational oncology therapies, contact the FDA’s Project Facilitate.

Source: FDA