Merck's Welireg Scores Big in Kidney Cancer Trials, Bolstering Post-Keytruda Strategy

Merck & Co. has announced significant breakthroughs in two Phase 3 trials for its kidney cancer drug Welireg, potentially expanding its use and solidifying the company's position in oncology as it prepares for life after Keytruda's patent expiration.

Welireg-Keytruda Combo Shows Promise in Adjuvant Setting

In a major development for kidney cancer treatment, Merck reported that the combination of Welireg and Keytruda demonstrated a statistically significant and clinically meaningful improvement in disease-free survival compared to Keytruda alone in patients with clear cell renal cell carcinoma (RCC) following surgical removal of cancerous tissue.

This success in the adjuvant setting could prove particularly lucrative for Merck. Leerink Partners analyst Daina Graybosch estimates that approval in this indication could potentially triple Merck's annual U.S. revenue opportunity from $2.3 billion to $6.3 billion by 2029, even after Keytruda loses market exclusivity.

The trial, known as LITESPARK-022, will continue to assess overall survival as a key secondary endpoint. Merck plans to present detailed results at upcoming medical meetings and submit the data to global regulatory authorities.

Welireg-Lenvima Combination Shows Mixed Results

In a separate Phase 3 trial, LITESPARK-011, the combination of Welireg and Eisai's Lenvima met one of its primary endpoints, showing a statistically significant improvement in progression-free survival compared to Exelixis' Cabometyx in advanced RCC patients whose disease progressed after PD-1/L1 therapy.

However, the results were not unequivocally positive. While a trend toward improvement in overall survival was observed, it had not reached statistical significance at the time of an interim analysis. This mixed outcome may pose challenges for regulatory approval and physician adoption, given the potential for increased toxicity with the Welireg-Lenvima combination compared to Cabometyx monotherapy.

Merck's Post-Keytruda Strategy Takes Shape

These trial successes come at a crucial time for Merck as it prepares for the loss of exclusivity for its blockbuster immunotherapy Keytruda, expected later this decade. Welireg, acquired through Merck's 2019 buyout of Peloton Therapeutics, is one of several drugs the company is counting on to sustain growth in the post-Keytruda era.

Welireg, which targets the HIF-2 alpha protein, has steadily expanded its indications since its initial FDA approval in 2021 for tumors associated with von Hippel-Lindau disease. It has since gained approvals in kidney cancer and rare adrenal tumors, with sales reaching $300 million in the first half of 2025.

Merck CEO Robert Davis has expressed confidence in the company's pipeline, citing approximately 20 additional new growth drivers with blockbuster potential in the coming years. This includes recent acquisitions such as the $10 billion buyout of Verona Pharma, which added Ohtuvayre, a first-in-class drug for chronic obstructive pulmonary disease, to Merck's portfolio.

As Merck navigates the transition away from its reliance on Keytruda, which generated $29.5 billion in sales last year, the company is also implementing a cost-cutting program aimed at saving $3 billion annually by the end of 2027. This strategy includes a reduction of about 6,000 jobs, underscoring the challenges and opportunities that lie ahead for one of the pharmaceutical industry's leading players.