Merck’s WELIREG meets primary endpoint of PFS in Phase 3 RCC trial

Global pharmaceutical leader Merck has announced that WELIREG (belzutifan), its pioneering oral HIF-2α inhibitor, has achieved a critical milestone in its Phase 3 trial LITESPARK-005. The trial, conducted on adult patients with advanced renal cell carcinoma (RCC) that progressed following PD-1/L1 checkpoint inhibitor and VEGF-TKI therapies, met its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to everolimus.

Based on a pre-specified interim analysis by an independent Data Monitoring Committee, WELIREG demonstrated its potential as an effective treatment option for patients with advanced renal cell carcinoma. While a statistically significant improvement was observed in the trial’s key secondary endpoint of objective response rate (ORR), the overall survival (OS) trend showed positive directionality but did not reach statistical significance. OS will be further evaluated in a subsequent analysis.

Dr. Marjorie Green, senior vice president and head of late-stage oncology at Merck Research Laboratories, highlighted the unmet need for new treatment options for advanced renal cell carcinoma patients, particularly those who don’t respond to PD-1/L1 and VEGF-TKI therapies. “WELIREG’s Phase 3 trial is groundbreaking,” Green stated, “This is the first trial showing positive results in advanced RCC post these therapies and the first novel mechanism demonstrated in recent years. We eagerly anticipate discussing these encouraging results with health authorities.”

WELIREG, as the first HIF-2α inhibitor therapy, was approved in the U.S. for the treatment of adult patients with von Hippel-Lindau (VHL) disease associated with renal cell carcinoma and other conditions. Currently, it has gained regulatory approvals in multiple countries, including the U.S., Canada, and Great Britain. Further global applications are under review based on data from the Phase 2 LITESPARK-004 trial.

The LITESPARK-005 trial is a randomized, open-label Phase 3 trial that evaluated WELIREG against everolimus in the treatment of advanced RCC patients with prior PD-1/L1 and VEGF-TKI therapies. The dual primary endpoints were PFS and OS. Secondary endpoints included ORR, DOR, and safety and tolerability. The trial enrolled 746 patients, randomized to receive either WELIREG or everolimus.

Merck’s achievement in meeting the primary endpoint in its Phase 3 trial showcases the promise of WELIREG in providing an effective treatment option for advanced renal cell carcinoma patients, potentially transforming the renal cell carcinoma therapy landscape.