Merck's Welireg Secures Third FDA Approval, Expanding Treatment Options for Rare Endocrine Tumors

Merck's hypoxia-inducible factor-2 alpha (HIF-2a) inhibitor, Welireg (belzutifan), has received its third FDA approval, marking a significant milestone in the treatment of rare endocrine system tumors. The latest indication covers patients aged 12 and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL), positioning Welireg as the first oral treatment for advanced PPGL.

Expanding Treatment Landscape for PPGL

The FDA's decision to approve Welireg for PPGL addresses a critical unmet need in the treatment of these rare tumors. Pheochromocytomas form inside the adrenal gland, while paragangliomas develop along but outside the adrenal gland, often near the aorta or carotid artery. These tumors can lead to life-threatening high blood pressure and pose significant diagnostic and treatment challenges due to their complexity and rarity.

Dr. Camilo Jimenez of the University of Texas MD Anderson Cancer Center highlighted the importance of this approval, stating, "Welireg could represent a change to the treatment paradigm for eligible patients," as it offers a non-surgical option for PPGL. With an estimated 2,000 new cases diagnosed annually in the U.S. and 52,800 globally, this approval provides a valuable treatment alternative for patients requiring specialized care.

Clinical Efficacy and Patient Outcomes

The label expansion is supported by results from the phase 2 LITESPARK-15 single-arm study, which enrolled 72 patients. The trial met its primary endpoint, with 26% of patients achieving partial or complete response to treatment. Notably, the median duration of response was 20.4 months, meeting a key secondary measure. Additionally, 32% of patients on baseline blood pressure medications were able to reduce their use by at least 50% for a minimum of six months, demonstrating Welireg's potential to improve quality of life for PPGL patients.

Welireg's Journey and Future Prospects

Merck acquired belzutifan through its $1.1 billion takeover of Peloton Therapeutics in 2019, with an additional $1.2 billion in potential milestone payments. Since then, Welireg has secured FDA approvals for von Hippel-Lindau disease in 2021 and renal cell carcinoma (RCC) in 2023. The RCC indication, in particular, has been a significant driver of Welireg's commercial success, with sales more than doubling from $218 million in 2023 to $509 million in 2024.

As Merck continues to explore Welireg's potential, ongoing clinical trials are investigating its efficacy in glioblastoma multiforme, potentially paving the way for a fourth indication. With its unique mechanism of action and growing list of approved indications, Welireg is poised to become a key player in Merck's oncology portfolio and a valuable treatment option for patients with rare and difficult-to-treat cancers.