Merck & Co. has scored an FDA approval for its blockbuster-to-be Welireg to move into second-line treatment of kidney cancer.
Originally approved as a third-line option, Welireg has now won the FDA’s blessing to be used alongside Merck’s Eisai-partnered Lenvima in second-line renal cell carcinoma with a clear cell component (ccRCC) following a PD-(L)1 inhibitor.
Analysts at Leerink Partners and William Blair have projected rapid uptake for Welireg in the indication based on data from the phase 3 Litespark-011 trial and doctors’ feedback. Welireg’s entry in second-line kidney cancer could put some pressure on Exelixis’ Cabometyx, which is also used together with Bristol Myers Squibb’s Opdivo as a first-line treatment.
In an interview in May, Katy Beckermann, M.D., Ph.D., director of genitourinary cancer research at Tennessee Oncology, told William Blair analysts that she views the Litespark-011 results as practice-changing, according to a May 4 note.
In the study, Welireg-Lenvima reduced patients’ risk of progression or death by 26% compared with Cabometyx. The combo extended median progression-free survival by four months to 14.6 months. Although the final overall survival analysis did not show a statistically significant benefit, the result favored the combo as patients lived a median 33.7 months, versus 28.6 months in the control arm.
Welireg and Lenvima also showed higher tumor response rate, at 53%, than Cabometyx did at 40%. Beckermann pinned her excitement instead on a nearly doubling of duration of response to 23 months versus 12 months.
Similarly, in a March note following presentation of detailed Litespark-011 results, Leerink analysts projected rapid uptake for the combo in the second-line setting “based on compelling survival and durability outcomes that showed little detriment in toxicity and quality of life” compared with Cabometyx.
Both Cabometyx and Lenvima are multi-target tyrosine kinase inhibitors that have been used in second-line kidney cancer. Now, Welireg adds a new mechanism as the first-in-class HIF-2α inhibitor. The drug was first approved in December 2023 for kidney cancer patients who have progressed on a PD-(L)1 inhibitor and a VEGF TKI.
While experts predict rapid uptake for Welireg in the second line, the Merck drug won’t be able to target first-line patients just yet following a surprise phase 3 failure in the Litespark-012 trial earlier this year.
Both Leerink and William Blair analysts have predicted a slow rollout for Welireg in the adjuvant setting after an FDA expansion in June. Despite a disease-free survival win from the Litespark-022 trial of Welireg and Keytruda as an adjuvant therapy, Beckermann said she would like to see more mature overall survival data, especially given the regimen’s added toxicities, according to William Blair.
Merck could make up for those shortfalls in the future. Through a collaboration signed in 2024, Merck is testing Welireg with Exelixis’ next-generation TKI zanzalintinib. The phase 3 Litespark-033 trial was recently launched for that combo in recurrent ccRCC during or after adjuvant PD-(L)1 therapy.