WELIREG® (belzutifan) Gains First European Commission Approval for Two Uses

Merck, also recognized as MSD outside the U.S. and Canada, has announced the conditional approval of its oral drug WELIREG (belzutifan) by the European Commission (EC). This approval marks a significant milestone as WELIREG becomes the first oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor to receive approval in the European Union. WELIREG is now sanctioned for use as a monotherapy in adult patients with specific types of von Hippel-Lindau (VHL) disease-associated tumors and those with advanced renal cell carcinoma (RCC) that have progressed following prior treatments.

The green light from the EC was granted following results from the LITESPARK-004 and LITESPARK-005 clinical trials. These studies demonstrated the efficacy of WELIREG in its approved indications, providing a new therapeutic option for patients with VHL disease-associated tumors and advanced RCC. In particular, WELIREG offers an alternative for patients with VHL tumors who cannot undergo localized procedures and for those with advanced RCC who have not responded adequately to a PD-1 or PD-L1 inhibitor and at least two VEGF-targeted therapies.

WELIREG's approval covers all 27 EU member states and extends to Iceland, Liechtenstein, and Norway. As it holds conditional approval, continuation is contingent upon yearly renewals based on additional clinical data. Availability across different EU countries will vary depending on the completion of national reimbursement procedures.

In the LITESPARK-004 trial, WELIREG is highlighted as the sole systemic treatment for certain VHL disease-associated tumors, showcasing significant objective response rates (ORR) and duration of response (DOR). For patients involved in the study with VHL disease-associated RCC, WELIREG showed an ORR of 49%, with partial responses observed. Notably, the responses were ongoing, indicating durability beyond 22 months in some cases. The treatment was similarly effective in patients with VHL-associated CNS hemangioblastomas and pancreatic neuroendocrine tumors (pNET), with high ORRs and durable responses.

The LITESPARK-005 trial spotlighted WELIREG's potential in advanced RCC cases. Here, WELIREG reduced the risk of disease progression or death by 25% compared to everolimus, highlighting its role in extending progression-free survival among patients with treatment-resistant advanced RCC. The trial's results emphasized WELIREG's potential to improve outcomes in a challenging patient population, providing a therapeutic alternative where options have been limited.

WELIREG's introduction in the EU brings hope to patients affected by VHL disease and advanced RCC, conditions where treatment advancements are crucial. The drug’s approval underscores Merck's commitment to pioneering therapeutic solutions in oncology, striving to address unmet medical needs and enhance patient care through scientific innovation.

This development further cements WELIREG's status as a groundbreaking treatment option, having already received approval in other regions, including the U.S., where it was sanctioned for similar indications. The approval in the EU represents another step forward in expanding access to this novel therapy, potentially improving quality of life and clinical outcomes for patients facing these complex diseases.