Merck's First-in-Class HIF-2α Inhibitor Welireg Approved by FDA for Advanced Renal Cell Carcinoma with Significant PFS Improvement

▎WuXi

Edited by Kant Content Team

MSD recently announced that the U.S. FDA has approved the supplemental New Drug Application (sNDA) for its "first-in-class" hypoxia-inducible factor-2α (HIF-2α) inhibitor Welireg (belzutifan) for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have experienced disease progression following treatment with a PD-1/PD-L1 inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI).According to the press release, Welireg is the first HIF-2α inhibitor approved for patients with advanced RCC, and this approval of Welireg also marks the first new class of drugs approved for this patient population since 2015.

This approval is based on the statistically and clinically significant results of LITESPARK-005. LITESPARK-005 is the first study specifically evaluating disease progression in patients who received PD-1 or PD-L1 inhibitors and VEGF-TKI treatments.EveningPeriod RCCThe patient's trial. In this trial,Compared with everolimus, Welireg significantly improved progression-free survival (PFS) in patients, reducing the risk of disease progression or death by 25% (HR=0.75, 95% CI: 0.63-0.90; p=0.0008).Patients in the Welireg groupObjective Response Rate (ORR)The ORR was 22% (95% CI: 18-27), with a complete response (CR) rate of 3% and a partial response (PR) rate of 19%. In the everolimus group, the ORR was 4% (95% CI: 2-6), with no patients achieving CR and a PR rate of 4%.

Welireg is the first HIF-2α inhibitor to receive FDA accelerated approval, which has currently been approved in the United States, the United Kingdom, Canada, and several other countries and regions, based on the ORR and duration of response (DOR) data from the Phase 2 LITESPARK-004 trial, for the treatment of relevant RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors, and adult patients with von Hippel-Lindau (VHL) disease who do not require immediate surgery.

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References:

[1] FDA Approves Merck’s WELIREG® (belzutifan) for theTreatment of Patients With Advanced Renal Cell Carcinoma (RCC) Following a PD-1or PD-L1 Inhibitor and a VEGF-TKI. Retrieved December 14, 2023 from https://www.merck.com/news/fda-approves-mercks-welireg-belzutifan-for-the-treatment-of-patients-with-advanced-renal-cell-carcinoma-rcc-following-a-pd-1-or-pd-l1-inhibitor-and-a-vegf-tki/

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