Welireg Improves Survival in Advanced Kidney Cancer

The use of Welireg (belzutifan) has been shown to significantly improve survival without disease progression in patients with advanced renal cell carcinoma (RCC), the most common type of kidney cancer, according to preliminary results from a phase 3 trial.

Welireg is an oral hypoxia-inducible factior-2 alpha (HIF-2α) inhibitor to treat adult patients with von Hippel-Lindau disease (VHL; a rare genetic multi-system disorder, in which non-cancerous tumors may grow in specific parts of the body) who need therapy for diseases including renal cell carcinoma, according to a press release from Merck, the manufacturer of the drug. In 2021, the U.S. Food and Drug Administration approved the use of Welireg for adult patients with VHL disease who require treatment for RCC, central nervous system hemangioblastomas and pancreatic neuroendocrine tumors that do not require immediate surgery.

According to the press release, Welireg was the first HIF-2α inhibitor therapy that has been approved in the U.S..

RCC is that most common type of kidney cancer, as stated in the press release, and is approximately twice as common in men compared with women. The press release also acknowledged that approximately 15% of patients in the U.S. with kidney cancer receive a diagnosis at an advanced stage.

Merck’s phase 3 trial, LITESPARK-005, is evaluating Welireg as a treatment for adults with advanced RCC that has worsened after the use of PD-1/L1 checkpoint inhibitor and vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) therapies.

These preliminary findings demonstrated that the use of Welireg significantly improved progression-free survival (PFS, the period during and after treatment of cancer when the disease does not worsen) compared with Afinitor (everolimus), a medication that treats certain types of cancer by increasing the activity of an immune system or prevents kidney rejection. PFS was the trial’s primary endpoint, which is a main result that measures a treatment’s efficacy in a study.

“Patients with advanced RCC face low survival rates, and for those whose cancer progresses following PD-1/L1 and VEGF-TKI therapies, there is a need for new treatment options that can reduce their risk of disease progression or death,” Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development at Merck Research Laboratories, said in the press release. “This is the first phase 3 trial to show positive results in advanced RCC following these therapies and the first new mechanism to demonstrate potential in advanced RCC in recent years. We look forward to discussing these results with health authorities.”

Researchers also assessed overall survival (the period from diagnosis or treatment where patients are still alive) in the trial, in which Merck noted a rise toward improvement that has yet to reach statistical significance.

As for the objective response rate, defined as the percentage of the treatment group who have a partial or complete response to treatment within a given period, was met as the trial’s secondary endpoint.

The most significant warning related to treatment with Welireg was embryo-fetal toxicity. Exposure to Welireg during pregnancy can harm the embryo-fetus, and it is necessary to verify pregnancy status before starting the treatment, the release noted.

Welireg’s side effect profile was established in a previous phase 2 trial, LITESPARK-004. The respective trial found that severe side effects included anemia, hypoxia (low levels of oxygen in body tissues), allergic reaction, retinal detachment and central retinal vein occlusion. The release noted that these severe side effects occurred in one patient each, totaling 15% of patients in the trial.

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