On blockbuster mission, Merck says Welireg hit endpoint in renal cell carcinoma trial

Two years after Welireg's original approval in the rare von Hippel-Lindau (VHL) disease, Merck is looking to expand its drug's reach and turn it into a blockbuster.

The drug, which Merck picked up through its $1.1 billion buyout of Peloton Therapeutics in 2019, showed improvements in progression-free survival among certain renal cell carcinoma (RCC) patients in a phase 3 trial comparing it with Novartis’ Afinitor.

Specifically, investigators tested the oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor in patients with advanced RCC that progressed following treatment with a PD-1/L1 checkpoint inhibitor and a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) therapy.

Welireg also demonstrated a statistically significant improvement in objective response rate, plus a trend toward improvement in overall survival (OS) that didn’t reach statistical significance, Merck said. The company added that it will look at OS in a future analysis.

The trial is the first to show positive results in advanced RCC following prior treatment with a checkpoint inhibitor and a VEGF-TKI therapy, according to Merck Research Laboratories senior vice president and late-stage oncology head Marjorie Green, M.D. It's also the first new mechanism of action in recent years to demonstrate potential in the disease, Green said.

“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,” Green said in a statement.

The study, called LITESPARK-005, is one of four phase 3 trials assessing Welireg’s potential in RCC.

Welireg’s original approval in 2021 came about a month ahead of its expected FDA decision date with a slightly broader label than originally expected, covering VHL disease patients who need therapy for associated RCC, central nervous system hemangioblastomas or pancreatic neuroendocrine tumors not requiring immediate surgery. It was a welcome addition to Merck’s oncology portfolio as it works to differentiate the company's business from star Keytruda and its looming 2028 patent cliff.

If Welireg expands into the broader RCC use, the drug could generate the type of momentum Merck is hoping to see. Before the drug's original approval, the company had "publicly highlighted belzutifan as a blockbuster opportunity," Cantor Fitzgerald analysts said in a note at the time, referring to the drug's generic name.

Welireg generated $92 million in the first half of the year, up considerably from $40 million during all of 2022.