New oral indication of Bestifan approved, marking another breakthrough in the treatment of pheochromocytoma and paraganglioma

On year5 month14 day, 2025, Merck (Merck) announced that its independently developed oral small molecule drug bezutifan (belzutifan, trade name Welireg) has obtained approval from the U.S.FDAApproved for the treatment of pheochromocytoma (Pheochromocytoma< /span>) or paraganglioma (Paraganglioma, referred to as PPGL) patients. This approval not only marks the FDA's first oral treatment for this type of tumor, but also brings new hope to some patients who have no possibility of surgical treatment.

Bestifan is an oral HIF-2α (hypoxia-inducible factor 2α) selective inhibitor that interferes with the HIF pathway, thereby inhibiting tumors that rely on this pathway. The drug was initially approved by the FDA in 2021 for the treatment of tumors related to Hipper-Lindau syndrome (VHL syndrome), and was approved in 2023 The indications have been expanded in pan> to include patients with advanced renal cell carcinoma (RCC) who have previously received PD-1 or PD-L1 inhibitors and VEGF-TKI treatment. The new indication obtained this time is an important milestone in the further expansion of its treatment field.

FDAThis approval is based onLITESPARK-015 IIData results from phase-1 clinical studies. The study was an open-label, multi-cohort design study that enrolled a total of 72 patients with locally advanced or metastatic PPGL. The study requires patients to have well-controlled blood pressure and no indications for surgery or radical treatment. In the trial, all patients took 120 mg of belzutifan orally once a day and were treated until the disease progressed or intolerable side effects occurred. The primary endpoint of the study is objective response rate (ORR), which was evaluated by an independent review committee in accordance with RECIST 1.1 standards.

The trial results showed that the objective response rate of the drug was 26% (95% CI: 17%-38%), the median response duration was 20.4 months, and more than half of the responders' response lasted for at least one year. It is worth noting that 60 patients in the study originally needed to use antihypertensive drugs, and 19 people (approximately 32%) had their antihypertensive drug use reduced by at least half, and the duration reached 6 or more. This suggests that while controlling tumors, bestivan may also be helpful in alleviating the symptoms of hypertension associated with PPGL.

In terms of safety, common adverse reactions include anemia, fatigue, muscle pain, dizziness, nausea, dyspnea, etc., most of which are mild to moderate. According to label recommendations, the daily dose for adults is 120mg taken orally once, and the same is true for adolescents weighing ≥40kg. For patients weighing <40kg, the recommended dose is 80mg once daily. Treatment will continue until disease progression or unacceptable adverse effects occur.

The approval of this new indication not only fills the gap in the field of drug treatment of pheochromocytoma and paraganglioma, but also further affirms the potential ofHIF-2α inhibitors in solid tumors. In the future, as the demand for the treatment of rare tumors increases globally, bezotivan may continue to expand its application prospects in the treatment of more solid tumors.

Reference:US Food and Drug Administration. FDA approves belzutifan for pheochromocytoma or paraganglioma. May 14, 2025.