FDA Approves Merck's Welireg for Rare Tumors PPGL

Merck & Co, operating as MSD outside North America, has achieved a significant milestone with the recent approval of its drug, Welireg (belzutifan), by the United States Food and Drug Administration (FDA). This approval marks the arrival of the first oral treatment specifically designed for pheochromocytoma and paraganglioma (PPGL), two rare and challenging tumor types. The green light from the FDA allows the administration of Welireg to both adult and pediatric patients aged 12 years and older who have locally advanced, unresectable, or metastatic PPGL.

Pheochromocytoma and paraganglioma, sometimes collectively referred to as "pheo par," are rare tumors that affect nearly 2,000 new individuals annually in the United States. Characteristically, pheochromocytoma originates in the adrenal gland, while paraganglioma develops outside of it. Both conditions can arise due to genetic syndromes or mutations, presenting significant challenges in terms of treatment and management.

Merck's acquisition of Welireg traces back to 2019, when the company acquired Peloton Therapeutics for $1.1 billion. The drug operates by inhibiting the transcription factor hypoxia-inducible factor 2 alpha (HIF-2α), a key regulator of cellular proliferation, angiogenesis, and tumor growth. Previously, Welireg had been approved in the United States for patients with von Hippel-Lindau (VHL) disease and renal cell carcinoma (RCC), underscoring its versatility in treating cancer-related conditions.

The recent FDA decision to approve Welireg for PPGL was heavily supported by the findings from the phase 2 LITESPARK-015 clinical trial. This study involved 72 patients, all of whom had measurable disease, a confirmed histopathological diagnosis of PPGL, and advanced or metastatic conditions not suitable for surgery or curative treatments. Notably, the trial demonstrated an objective response rate of 26% in patients treated with Welireg, with a median response duration of 20.4 months. Furthermore, among patients who were on antihypertensive medications at the start of the trial, 32% experienced a significant reduction in at least one antihypertensive medication by 50% or more for a duration of at least six months.

Marjorie Green, Merck Research Laboratories' senior vice president and head of oncology in global clinical development, emphasized the significance of this approval. She highlighted the historical lack of approved systemic treatment options for patients suffering from advanced PPGL, pointing out the critical role this new treatment could play in managing the disease in the United States.

The approval of Welireg for PPGL patients in the U.S. closely follows the European Commission's decision to grant conditional approval for the drug in the treatment of VHL disease and RCC. This previous decision introduced Welireg as the first systemic treatment for adult patients with certain VHL disease-associated tumors when localized procedures were not feasible. It also provided a new opportunity for adult patients with advanced clear cell RCC, particularly those whose condition progressed after treatment with a PD-1 or PD-L1 inhibitor and at least two VEGF-targeted therapies.

Overall, Merck's Welireg represents a promising advancement in the treatment landscape for rare tumors like PPGL, offering new hope and options for patients whose conditions are particularly difficult to manage with existing therapies. This latest approval underscores Merck's ongoing commitment to addressing unmet medical needs and enhancing therapeutic possibilities for patients with rare and complex cancers.