Dive Brief:

• A three-drug combination involving Merck & Co.’s Welireg failed to significantly delay tumor progression or extend survival in a Phase 3 trial of patients newly diagnosed with the most common form of kidney cancer, setting back the big drugmaker’s plans to further expand use of the medication.
• The study evaluated Welireg alongside Merck’s immunotherapy Keytruda and Eisai’s Lenvima in first-line clear cell renal cell carcinoma and compared that regimen to the Keytruda-Lenvima tandem alone. Merck didn’t provide specifics, but said that drug trio — as well as a separate one also tested in the trial — missed the study’s dual main objectives at an interim analysis.
• Merck noted how the findings don’t affect other ongoing studies in “Litespark,” the broad program it’s jointly conducting with Eisai and that includes other Welireg tests. The Food and Drug Administration is reviewing an application based on results from one Litespark study that would expand use of Welireg earlier in kidney cancer. Still, Merck shares fell by about 4% Tuesday.

Dive Insight:

Welireg is an important part of Merck’s plan to absorb the coming losses when Keytruda, the company’s top moneymaker, loses patent exclusivity.

Acquired through a buyout of Peloton Therapeutics in 2019, Welireg blocks a protein called HIF-2 alpha that’s known as a primary driver of clear cell renal cell carcinoma. Since then, the drug has racked up approvals in a rare genetic condition, an uncommon adrenal tumor and, importantly for Merck, made headway into advanced kidney cancer.

Those clearances have made Welireg one of Merck’s faster-ascending medicines and a highlight in its strategy to hit $70 billion in annual sales by next decade. Welireg sales grew more than 40% in 2025, surpassing Wall Street expectations to reach $716 million for the year. Anticipated label expansions into the second-line and post-surgery settings should drive revenues even higher.

Yet Tuesday’s study result significantly lowers the drug’s financial ceiling. To Leerink Partners analyst Daina Graybosch, the failure takes Merck’s “upside case” for filling the Keytruda revenue gap in the early 2030s “off the table.” Consensus estimates have projected about $2.2 billion in global sales for Welireg in 2030. But success in first-line kidney cancer could have unlocked $5.8 billion in overall revenue potential given how long patients stay on therapy when Welireg works, Graybosch wrote.

The setback could have implications for others, too. Arcus Biosciences is developing a rival HIF-2 alpha medicine in kidney cancer and, by the end of the year, intends to start a Phase 3 trial in the first-line setting. Mizuho Securities analyst Salim Syed noted that Arcus’ medicine may be a “superior” molecule based on earlier data. The regimen Arcus is expected to test is also different, sparing use of a “tyrosine kinase” inhibitor like Lenvima that may add toxicity, Syed wrote.

Welireg’s failure leaves a “potential [first-line] opening” for Arcus’ drug, casdatifan, added Cantor Fitzgerald’s Li Watsek.

Arcus shares ticked up about 2% Tuesday.