FDA-Approved Belzutifan Offers New Hope for Neuroendocrine Tumors

A multicenter Phase II clinical trial, spearheaded by researchers at The University of Texas MD Anderson Cancer Center, has shown promising results in treating patients with advanced pheochromocytoma and paraganglioma (PPGL) — two rare, aggressive, and potentially life-threatening neuroendocrine tumors. (1^✔ ✔Trusted Source
Belzutifan for Advanced Pheochromocytoma or Paraganglioma

Go to source) The study demonstrated substantial tumor shrinkage and effective disease control, offering new hope for patients facing these challenging malignancies and highlighting the potential of emerging therapeutic strategies in managing rare neuroendocrine cancers.

The results of this study, led by Camilo Jimenez, M.D., professor of Endocrine Neoplasia and Hormonal Disorders, were published in the New England Journal of Medicine and presented concurrently at the 2025 European Society for Medical Oncology (ESMO) Congress (Abstract 1705O).

Belzutifan Achieves 26% Objective Response Rate with Sustained Benefit in Rare Cancers

The trial demonstrated that the HIF-2α inhibitor belzutifan showed meaningful antitumor activity with a 26% objective response rate, a significant achievement particularly for rare and difficult-to-treat cancers. These effects lasted an average of more than 20 months, indicating a sustained clinical benefit for those who responded to treatment.

It’s notable that nearly one-third of patients (32%) who were taking blood pressure medication were able to reduce their dosage by half for at least six months. This is an important finding, as PPGL tumors often produce excess hormones that raise blood pressure. These results suggest that belzutifan may have also helped manage symptoms related to hormone-secreting tumors.

“The primary significance of this study is demonstrating that HIF-2α inhibition with belzutifan can achieve meaningful clinical benefit in patients with advanced, progressive PPGL,” Jimenez said. “In a population with no remaining standard-of-care options, we observed durable disease control and a manageable safety profile, supporting the rationale for HIF-2α as a therapeutic target in this rare tumor type.”

Pheochromocytoma and paraganglioma (PPGL) are difficult-to-treat cancers that affect roughly 2,000 people annually in the U.S. One of the main drivers of tumor growth in PPGL is the HIF-2α protein.

In healthy cells this protein adjusts to changes in oxygen levels, but genetic mutations or changes in cell metabolism can cause HIF-2α to become abnormally active, triggering signals that help the tumor grow and spread.

HIF-2α inhibitors, such as belzutifan, have been successful in shrinking tumors and slowing disease progression in other cancers driven by HIF-2α overactivity, such as kidney cancer and von Hippel-Lindau (VHL) disease. Building on this knowledge, researchers evaluated the effectiveness of these inhibitors in patients with advanced PPGL.

On the LITESPARK-015 Phase II trial, 72 patients with locally advanced, metastatic, unresectable PPGL who had exhausted all other standard-of-care treatment, were treated with belzutifan.

First Oral Therapy for PPGL Patients Aged 12+

In May 2025, the Food and Drug Administration (FDA) approved belzutifan for the treatment of adult and pediatric patients ages 12 years and older with advanced, unresectable, or metastatic PPGL who do not require immediate surgery. Belzutifan is the first oral and only approved therapy for this disease, making it a new standard of care for this patient population.

“The approval of belzutifan offers new hope. As an oral treatment, it has been shown to shrink tumors, reduce symptoms, and improve quality of life with low toxicity. It represents a meaningful step forward in care for people living with these rare cancers,” Jimenez said.

2025 – FDA approves belzutifan for treatment of adult and pediatric patients 12 years and older with PPGL.

2023 – FDA approves belzutifan for advanced renal cell carcinoma (RCC) after treatment with a PD‑1/PD‑L1 inhibitor and a VEGF tyrosine kinase inhibitor (VEGF‑TKI).

2021 - FDA approves belzutifan for adults with von Hippel‑Lindau (VHL) disease who require treatment for associated tumors (RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors), when surgery is not immediately necessary.

Reference:

1. Belzutifan for Advanced Pheochromocytoma or Paraganglioma - (https://www.nejm.org/doi/full/10.1056/NEJMoa2504964)

Source-Eurekalert