Merck’s kidney cancer drug Welireg approved for second-line use with Lenvima

Welireg, a kidney cancer treatment from Merck (MSD), has been approved for use earlier in the treatment sequence.

According to Fierce Pharma on the 25th (local time), the U.S. Food and Drug Administration (FDA) approved Welireg in combination with Lenvima, developed jointly with Eisai, for second-line treatment of renal cell carcinoma with a clear cell component (ccRCC) after treatment with a PD-(L)1 inhibitor.

Welireg was previously approved as a third-line treatment. The decision moves it one step earlier in the treatment sequence.

Leerink Partners and William Blair analysts forecast rapid market uptake for Welireg, citing data from the phase 3 LITESPARK-011 trial and feedback from clinicians.

In the trial, the Welireg-Lenvima combination reduced the risk of disease progression or death by 26% compared with Cabometyx. Median progression-free survival was extended by 4 months to 14.6 months.

Overall survival did not differ significantly, but was 33.7 months in the combination group, longer than the 28.6 months in the control group.

The tumor response rate was also higher with the combination, at 53%, than with Cabometyx, at 40%. The duration of response was 23 months, about twice the 12 months with Cabometyx.

William Blair reported that Katie Beckerman, M.D., of Tennessee Oncology described the LITESPARK-011 results as “practice-changing.”

Cabometyx and Lenvima are both multitargeted tyrosine kinase inhibitors (TKIs) that have been used as second-line treatments for kidney cancer. Welireg adds a new mechanism as the first HIF-2α inhibitor.

Welireg was first approved in December 2023 for patients with kidney cancer whose disease progressed after treatment with a PD-(L)1 inhibitor and a VEGF TKI.

However, Merck’s unexpected setback earlier this year in the first-line LITESPARK-012 trial has made Welireg’s entry into first-line treatment difficult for the time being.

Under a collaboration established in 2024, Merck is testing Welireg in combination with Exelixis’ next-generation TKI zanzalintinib. The phase 3 LITESPARK-033 trial in patients with recurrent ccRCC recently began.