Belzutifan Receives FDA Priority Review for Advanced Pheochromocytoma and Paraganglioma

The FDA accepted a supplemental new drug application (sNDA) for belzutifan (Welireg; Merck), an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, for priority review as treatment of advanced, unresectable, or metastatic pheochromocytoma and paraganglioma (PPGL) among adult and pediatric patients 12 years and older. Belzutifan has a Prescription Drug User Fee Act (PDUFA) date of May 26, 2025.¹

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“Pheochromocytoma and paraganglioma are rare tumors that form in and around the adrenal glands, and currently, there are no approved therapies available in the US for patients with this rare disease,” Marjorie Green, MD, senior vice president and head of oncology and global clinical development at Merck Research Laboratories, said in a news release.¹

Pheochromocytoma typically occurs in the center of the adrenal gland, whereas paraganglioma occurs in the nerve tissue in the adrenal glands and near specific blood vessels and nerves.¹

An estimated 2000 new cases of PPGL are diagnosed annually in the US, with around 52,800 new cases diagnosed globally.¹ Individuals with PPGL could present symptoms of high blood pressure, headache, heavy sweating, strong fast, or irregular heartbeat, being shaky, and being extremely pale—which could occur at any time or can be caused by certain events. However, researchers reported that various inherited disorders and changes in specific genes can increase the risk of PPGL. The disease reaches the metastatic stage when the cancer spread to another part of the body, occurring in up to 25% of PPGL cases.^1,2

The sNDA is based on objective response rate (ORR) and duration of response (DOR) results from the open-label, single-arm, multi-cohort phase 2 LITESPARK-015 (NCT04924075) that assessed the efficacy and safety of belzutifan monotherapy in individuals with advanced PPGL, and other advances solid tumors.^1,3

The study included a total of 322 individuals that received a 120 mg oral dose of belzutifan daily and were divided into 4 cohorts. Cohort A1 included individuals with advanced PPGL, cohort A2 included individuals with pancreatic neuroendocrine tumors (pNETs), cohort B1 included individuals with von hippel-lindau (VHL) disease-associated tumors, and cohort D included individuals with advanced solid tumors with HIF-2α-related genetic alterations.¹

The primary endpoint of the study includes ORR per Response Evaluation Criteria in solid tumors version 1:1 (RECIST v1:1) by blinded independent central review (BICR). Secondary endpoints include DOR, time to response, disease control, progression free survival, overall survival and safety, according to study authors.¹

Results from the study are expected to be presented at an upcoming medical meeting.¹

REFERENCES

1. FDA Grants Priority Review to Merck’s Application for WELIREG^® (belzutifan) for the Treatment of Patients With Advanced Pheochromocytoma and Paraganglioma (PPGL). Merck. News release. January 27, 2025. Accessed January 29, 2025. https://www.businesswire.com/news/home/20250127087005/en/FDA-Grants-Priority-Review-to-Merck%E2%80%99s-Application-for-WELIREG%C2%AE-belzutifan-for-the-Treatment-of-Patients-With-Advanced-Pheochromocytoma-and-Paraganglioma-PPGL

2. Pheochromocytoma and Paraganglioma Treatment (PDQ®)–Patient Version. NIH. News release. Accessed January 29, 2025. https://www.cancer.gov/types/pheochromocytoma/patient/pheochromocytoma-treatment-pdq#:~:text=Pheochromocytoma%20and%20paraganglioma%20are%20rare,adrenal%20paragangliomas%20are%20called%20paragangliomas

3. Belzutifan/​MK-6482 for the Treatment of Advanced Pheochromocytoma/​Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015). ClinicalTrials.gov. December 27, 2024. Accessed January 29, 2025. https://clinicaltrials.gov/study/NCT04924075