Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for the conditional approval of WELIREG® (belzutifan). This oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor has been recommended for use in two distinct indications:
- Von Hippel-Lindau (VHL) disease – WELIREG is recommended as a treatment for adult patients with VHL disease-associated tumors, including localized renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, and pancreatic neuroendocrine tumors (pNET), when localized treatments are unsuitable.
- Advanced renal cell carcinoma (RCC) – WELIREG is recommended for adult patients with advanced clear cell RCC who have progressed after two or more prior treatments, including a PD-1 or PD-L1 inhibitor and at least two vascular endothelial growth factor (VEGF)-targeted therapies.
The CHMP’s recommendation is now under review by the European Commission, with a final decision expected in the first quarter of 2025.
Dr. Marjorie Green, Senior Vice President at Merck, expressed her excitement about the positive opinion, noting that WELIREG represents the first-in-class HIF-2α inhibitor. She highlighted the importance of this treatment in addressing unmet needs in these patient populations in the European Union. If approved, WELIREG would be the only systemic treatment for patients with VHL disease-associated tumors in the EU.
The CHMP’s recommendation for VHL-associated tumors is based on data from the LITESPARK-004 trial, which demonstrated a significant objective response rate (ORR) and duration of response (DOR). In this trial, WELIREG showed promising results in patients with VHL-associated RCC, CNS hemangioblastomas, and pNET. For instance, in patients with VHL-associated RCC, WELIREG achieved a 49% ORR, with responses lasting up to 22 months. In CNS hemangioblastomas, the ORR was 63%, and in pNET, the ORR was 83%, showcasing the potential of WELIREG to address critical gaps in the treatment of VHL-associated tumors.
In advanced RCC, the CHMP’s recommendation is based on the LITESPARK-005 trial, which investigated WELIREG as a treatment for patients with RCC who had previously failed two lines of therapy, including PD-(L)1 inhibitors and VEGF-targeted therapies. The trial demonstrated that WELIREG reduced the risk of disease progression or death by 25% compared to everolimus. Furthermore, the ORR for WELIREG was 22%, compared to only 4% for everolimus, further validating its efficacy in advanced RCC.
Von Hippel-Lindau disease is a rare genetic condition affecting around 200,000 people worldwide, with RCC being the most common tumor type in these patients. Renal cell carcinoma, the most common form of kidney cancer, continues to be a major concern, with around 130,000 new cases diagnosed in Europe annually.
WELIREG (belzutifan) is already approved in the U.S. for treating adult patients with VHL disease-associated tumors and advanced RCC. It offers a novel mechanism of action for patients who have limited treatment options.
Merck is committed to advancing innovative therapies, and the positive CHMP opinion brings WELIREG one step closer to becoming an important treatment option for patients in the EU with unmet medical needs.
