FDA Approves Welireg for Advanced Kidney Cancer

The FDA has approved Merck’s Welireg (belzutifan), an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, to treat adult patients with advanced renal cell carcinoma (RCC). It is indicated for patients who have already been treated with a PD-1 or PD-L1 inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). As an inhibitor of HIF-2α, Welireg reduces transcription and expression of HIF-2α target genes associated with cellular proliferation, angiogenesis, and tumor growth.

Welireg was first approved in August 2021 to treat adult patients with tumors associated with von Hippel-Lindau (VHL) disease, a rare genetic disorder associated with an increased risk of developing certain tumors. The cost for Welireg oral tablet 40 mg is about $29,755 for a supply of 90 tablets, which is about a month’s supply, according to Drugs.com.

Renal cell carcinoma the most common type of kidney cancer. It is about twice as common in men than in women. About 15% of patients with kidney cancer are diagnosed at an advanced stage.

Toni K. Choueiri, M.D.

“Despite recent progress in the treatment of advanced RCC, there is yet to be an option specifically approved for patients whose disease progresses following a PD-1 or PD-L1 inhibitor and a TKI therapy,” Toni K. Choueiri, M.D., director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg professor of medicine, Harvard Medical School, said in a press release

Welireg’s approval in renal cell carcinoma based on results from LITESPARK-005 trial, in which Welireg demonstrated improvement in progression-free survival (PFS) in advanced RCC following treatment with both a PD-1 or PD-L1 checkpoint inhibitor and a VEGF receptor targeted therapy compared with the chemotherapy agent everolimus. Welireg showed an objective response rate of 22% compared with 4% for everolimus.

In the trial, Welireg reduced the risk of disease progression or death by 25% compared with everolimus. Among the 82 patients treated with Welireg who achieved a confirmed response, 25 (30%) patients had a duration of response ≥12 months. Overall survival results were immature. At the time of the pre-specified analysis, 59% of the patients had died in the randomized population.

Serious adverse reactions in those who received Welireg were hypoxia, anemia, pneumonia, hemorrhage and pleural effusion (water on the lungs). Fatal adverse reactions occurred in 3.2% of patients who received Welireg, including sepsis and hemorrhage. Permanent discontinuation due to adverse reactions occurred in 6% of patients.