FDA Approves Welireg for Pheochromocytoma and Paraganglioma

The FDA approved Welireg for those with locally advanced, unresectable or metastatic pheochromocytoma or paraganglioma: © stock.adobe.com.

The United States Food and Drug Administration (FS) approved Welireg (belzutifan) for adult and pediatric patients 12 years and older with locally advanced, unresectable or metastatic pheochromocytoma or paraganglioma (PPGL).

This is the first FDA approval of an oral therapy for the treatment of patients with PPGL. Moreover, this regulatory approval was based off study findings from the LITESPARK-015 trial.

In the trial, a total of 72 patients were treated in cohort A1, and in this cohort of patients, the overall response rate was 26%, and responses lasted a median of 20.4 months. Among 60 patients taking blood pressure medication, 32% were able to reduce at least one of their medications by half for six months or longer.

The most common side effects, affecting up to 25% of patients, included anemia, fatigue, muscle and joint pain, low lymphocyte and white blood cell counts. Additionally, there were changes in lab values such as elevated liver enzymes, calcium, potassium and alkaline phosphatase. Other side effects reported were shortness of breath, headache, dizziness and nausea.

The LITESPARK-015 trial was an open-label, multi-cohort study. Cohort A1 included evaluable participants with measurable disease confirmed by blinded independent central review, a documented diagnosis of pheochromocytoma or paraganglioma, and locally advanced or metastatic disease not suitable for surgery or curative treatment. Patients with controlled hypertension were eligible for trial enrollment if their blood pressure medications had remained stable for at least two weeks before starting the trial. Those with carcinomatous meningitis were excluded.

The recommended Welireg dose for adults is 120 milligrams taken by mouth once daily. For children 12 and older, dosing depends on body weight: those weighing 40 kilograms or more should also receive 120 milligrams daily, while those under 40 kilograms should receive 80 milligrams daily. Treatment should continue until the cancer worsens or side effects become unmanageable.

The main efficacy measure was objective response rate, as assessed by independent review using RECIST v1.1. Additional measures included duration of response and the number of patients who reduced at least one blood pressure medication by 50% or more for at least six months.

The FDA granted this application priority review and used the Assessment Aid, a voluntary tool submitted by the drugmaker to help streamline the review process.

Other approvals for this agent include an August 2021 approval. Welireg was approved by the FDA for the treatment of adult patients with von Hippel-Lindau disease who need treatment for their for renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors.

Moreover, in December 2023, the regulatory agency also approved Welireg for those with advanced renal cell carcinoma following treatment with a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI).

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