Merck, operating as MSD outside the US and Canada, revealed that the European Medicines Agency’s CHMP recommended conditionally approving Welireg (belzutifan), an oral inhibitor targeting hypoxia-inducible factor-2 alpha (HIF-2a), as a standalone treatment for:
- Adults with von Hippel-Lindau (VHL) disease needing intervention for localized renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), unsuitable for localized surgical options.
- Adults with advanced clear cell renal cell carcinoma (RCC) who have progressed following two or more therapy lines, including PD-1/PD-L1 inhibitors and at least two VEGF-targeted treatments.
This CHMP recommendation advances to the European Commission for marketing approval in the EU, with a conclusion anticipated in Q1 2025.
Dr. Marjorie Green, Merck Research Laboratories’ oncology head, commented, “Today’s promising CHMP endorsement nudges us closer to making Welireg available to select patients in Europe, crucially filling care gaps. We are dedicated to innovative treatments addressing significant global patient needs and await the European Commission’s ruling.”
The VHL Tumor CHMP Recommendation is anchored in objective response and duration findings from the LITESPARK-004 study. Approval would mark Welireg as the EU’s inaugural systemic treatment for VHL-associated tumors.
Approved in the US since August 2021, Welireg addresses VHL-related RCC, CNS hemangioblastomas, or pNETs requiring no immediate surgery, validated by the LITESPARK-004 clinical trial with 61 VHL-associated RCC patients. The trial reported a 49% objective response rate (ORR) among 61 patients, all partial responses, with a response duration exceeding 22 months in some cases; notably, 56% sustained responses for a year or more.
Enrolled patients showed other VHL-related tumors, like CNS hemangioblastomas and pNET. In CNS hemangioblastomas (n=24) within the trial, Welireg displayed a 63% ORR, with one complete response and a predominant partial response rate, continuing beyond 22 months. For pNET patients (n=12), Welireg revealed an 83% ORR, comprising two complete and eight partial responses, recognized with prolonged response preservation in half the cases for at least a year.
Advanced RCC Recommendation stemmed from progression-free survival (PFS) and ORR results from LITESPARK-005, the first positive Phase 3 RCC trial following PD-(L)1 and VEGF therapies.
As of December 2023, Welireg has U.S. approval for adults with advanced RCC treated post-PD-(L)1 and VEGF-targeted inhibitors, based on LITESPARK-005, involving 746 patients with resistant clear cell RCC. Results illustrated Welireg reducing disease progression risk by 25%. Median PFS matched at 5.6 months for Welireg and comparison therapy. Welireg achieved a 22% ORR with 3% complete and 19% partial responses, significantly outpacing the comparison’s 4%.
About VHL and RCC:
VHL disease, a rare genetic disorder, affects around 200,000 globally, including up to 15,000 in Europe. VHL patients face recurrent vascular tumors and certain malignancies like RCC, manifesting in 70% of affected individuals.
Renal cell carcinoma predominates kidney cancer forms, with over 130,000 European cases in 2020, twice more common in men. Notably, 30% of cases involve advanced stages.
US Indications for Welireg (belzutifan):
Designed for adults with von Hippel-Lindau disease necessitating RCC, CNS hemangioblastomas, or pNET therapy, Welireg refrains from requiring immediate surgery. It further serves adults with advanced RCC progressing post-treatment with PD-1/PD-L1 and VEGF-TKI inhibitors.