Merck’s Welireg Clears Phase III Primary Endpoint in Renal Cell Carcinoma
Pictured: Merck Research Laboratories headquarters in Silicon Valley/iStock, Michael Vi
Topline data from the Phase III LITESPARK-005 study showed that Merck’s Welireg (belzutifan) met its primary endpoint of a clinically meaningful improvement in progression-free survival in patients with advanced renal cell carcinoma, the company announced Friday.
Under a pre-specified interim analysis, an Independent Data Monitoring Committee found that patients treated with Welireg saw significantly better progression-free survival (PFS) compared with Novartis’ Afinitor (everolimus). Welireg also led to a significant improvement in objective response rate, a key secondary endpoint.
Merck’s oral HIF-2α inhibitor demonstrated an overall trend toward improvement in overall survival (OS), though this effect fell short of statistical significance. As for safety, Welireg’s adverse events in LITESPARK-005 were consistent with those observed in prior studies.
Patients with advanced renal cell carcinoma, especially those who have failed several prior lines of treatment, continue to suffer from low survival rates, Marjorie Green, Merck Research Laboratories’ head of late-stage oncology, global clinical development, said in a statement.
For these patients, “there is a need for new treatment options that can reduce their risk of disease progression or death,” Green said.
Merck did not provide specific data in its Friday news release but promised to do so at an upcoming medical congress. The company also plans to carry out further testing and analyses for OS, as well as share data from LITESPARK-005 with regulatory authorities.
Welireg is an orally available HIF-2α inhibitor that was approved in August 2021 for adults with the rare von Hippel-Lindau (VHL) disease who need treatment for associated malignancies such as renal cell carcinoma (RCC), central nervous system hemangioblastomas or pancreatic neuroendocrine tumors. Merck gained rights to the drug in May 2019 when it bought Peloton Therapeutics for around $1 billion in an upfront cash payment.
Welireg is the first ever therapy in this drug class to win the FDA’s approval. Its label comes with a boxed warning for embryo-fetal toxicities.
Beyond VHL disease, Merck is also evaluating Welireg in RCC, for which it is running four Phase III trials. The current LITESPARK-005 is a randomized and open-label trial with 746 enrolled patients whose RCC had progressed after treatment with a PD-1/L1 checkpoint inhibitor and a VEGF-TKI therapy. Its dual primary endpoints are PFS and OS.
Aside from LITESPARK-005, the company is also trialing Welireg in LITESPARK-011 and LITESPARK-012— which are evaluating the drug’s potential in the second line and treatment-naïve settings—and LITESPARK-022 in the adjuvant setting.