Merck scores USFDA OK for Welireg for 12 years and older with pheochromocytoma or paraganglioma

“PPGL, sometimes referred to as pheo para, is a rare condition affecting up to 2,000 people each year in the United States. Patients with these tumors, which arise from the adrenal glands and the extra-adrenal paraganglia, may require specialized care due to their complexity and rare nature, often posing significant challenges for both diagnosis and treatment,” said Dr. Camilo Jimenez, professor, department of endocrine neoplasia and hormonal disorders, The University of Texas MD Anderson Cancer Center. “This approval, which is based on objective response rate data from the LITESPARK-015 trial, introduces belzutifan as the only approved and available non-surgical option for locally advanced, unresectable, or metastatic PPGL and could represent a change to the treatment paradigm for eligible patients.”

“For patients with advanced PPGL, there has been a lack of approved systemic treatment options available to help manage their disease, underscoring the importance of this approval in the U.S.,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “This approval marks the third indication for WELIREG in the U.S. and demonstrates our company’s commitment to providing innovative cancer therapies for patients in need, including those with rare diseases.”

"The WELIREG label contains a boxed warning that exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective. WELIREG can cause severe anemia that can require a blood transfusion. Monitor for anemia before initiation of and periodically throughout treatment with WELIREG. WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. Monitor oxygen saturation before initiation of and periodically throughout treatment with WELIREG," the Company stated in a release.

LITESPARK-015 is an open-label, multicohort Phase 2 trial (ClinicalTrials.gov, NCT04924075) evaluating the efficacy and safety of WELIREG monotherapy. The study enrolled 72 patients in a single cohort (Cohort A1) who had measurable disease verified by blinded independent central review (BICR) per RECIST v1.1, documented histopathological diagnosis of PPGL, locally advanced or metastatic disease that was not amenable to surgery or curative treatment, and adequately controlled blood pressure (defined as BP <150/90 mm Hg, <135/85 mm Hg for adolescents) with no change in antihypertensive medications for patients with concomitant hypertension for at least two weeks prior to start of study treatment. Patients with carcinomatous meningitis were excluded. Patients received WELIREG at a dose of 120 mg once daily until disease progression or unacceptable toxicity.

The major efficacy outcome measure for the treatment of advanced PPGL was ORR measured by BICR using RECIST v1.1. Additional efficacy outcome measures included duration of response and time to response.

WELIREG (belzutifan) 40 mg tablets, indicated for oral use in the U.S. for adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

It is also indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) with a clear cell component following 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).