On November 13, 2026 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of WELIREG (belzutifan), Merck’s first-in-class oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, plus lenvatinib, the orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, for the treatment of adult patients with advanced renal cell carcinoma with a clear cell component (ccRCC) following a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This recommendation will now be reviewed by the European Commission (EC) for marketing authorization in the European Union (EU), Iceland, Liechtenstein and Norway. A final decision is expected in the next two months.

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"Patients with advanced renal cell carcinoma in the European Union have limited treatment options if their disease progresses following anti-PD-1 or anti-PD-L1 therapy," said Dr. Christina Derleth, vice president, global oncology clinical development, Merck Research Laboratories. "This positive opinion is a meaningful step toward potentially bringing this first-of-its-kind regimen to patients in need in the European Union and underscores the important role of WELIREG plus lenvatinib as a new option in the treatment of renal cell carcinoma."

The recommendation is based on results from the Phase 3 LITESPARK-011 trial. In the study, WELIREG in combination with lenvatinib demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), one of the study’s dual primary endpoints, reducing the risk of disease progression or death by 26% (HR=0.74 [95% CI, 0.61-0.89]; p=0.001) in patients with advanced ccRCC whose disease progressed on or after treatment with a PD-1 or PD-L1 inhibitor compared to cabozantinib. Initial results for the trial were presented at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium. At the final analysis, overall survival (OS), the study’s other dual primary endpoint, did not meet statistical significance for patients who received WELIREG in combination with lenvatinib compared to cabozantinib. WELIREG in combination with lenvatinib reduced the risk of death by 15% (HR=0.85 [95% CI, 0.70-1.03]) in these patients compared to cabozantinib. Additionally, at the final analysis, the combination showed a continued benefit in objective response rate (ORR), a key secondary endpoint, of 53.1% for WELIREG plus lenvatinib versus 40.2% for cabozantinib. Similarly, WELIREG in combination with lenvatinib improved duration of response (DOR), another secondary endpoint, compared to cabozantinib, with a median DOR of 22.0 months versus 11.9 months, respectively. These results were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2026.

In September 2026, WELIREG in combination with LENVIMA (lenvatinib) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with advanced ccRCC following a PD-1 or PD-L1 inhibitor, based on results from the Phase 3 LITESPARK-011 trial.

About LITESPARK-011
LITESPARK-011 is a randomized, open-label Phase 3 trial (ClinicalTrials.gov, NCT04586231) evaluating WELIREG in combination with LENVIMA compared to cabozantinib for the treatment of patients with advanced ccRCC. Eligible patients include participants with locally advanced or metastatic ccRCC who have progressed on or after a PD-1 or PD-L1 inhibitor, or within 6 months of completing adjuvant therapy with a PD-1 inhibitor. The trial enrolled 747 patients who were randomized to receive WELIREG (120 mg orally once daily) plus LENVIMA (20 mg orally once daily) or cabozantinib (60 mg orally once daily). The major efficacy endpoints were PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as assessed by blinded independent central review (BICR) and OS. Objective response rate per RECIST v1.1 as assessed by BICR, DOR per RECIST v1.1 as assessed by BICR and safety were additional endpoints.

About renal cell carcinoma
Renal cell carcinoma is the most common type of kidney cancer, with about nine out of 10 kidney cancer diagnoses being RCC. In 2024, there were an estimated 442,570 new cases of kidney cancer and 144,871 deaths from the disease worldwide. Renal cell carcinoma is about twice as common in men as in women. Cases of RCC might be discovered incidentally during imaging tests for other reasons. Approximately 32% of patients with kidney cancer are diagnosed at a regional or metastatic stage. Clear cell renal cell carcinoma, which accounts for about 70% of RCC diagnoses, is the most common subtype.

(Press release, Merck & Co, NOV 13, 2026, View Source [SID1234674750])