Merck gets two Welireg wins

Merck & Co has been trying to move its HIF-2α inhibitor Welireg into earlier renal cancer therapy lines, and today it boosted its hopes of this drug becoming a blockbuster, with positive topline results in the second-line and adjuvant settings.

The wins came in the phase 3 Litespark-011 and Litespark-022 trials respectively, with the company touting “clinically meaningful” benefits in both. However, one caveat is that Litespark-011 has only so far met one co-primary endpoint, progression-free survival. On the other co-primary of overall survival, the study has merely shown a trend towards a benefit, with evaluation continuing.

This echoes the result seen in the third-line Litespark-005 trial, which hit on PFS, but not OS. Still, this didn’t stop the FDA approving Welireg in December 2023 in renal cell carcinoma patients who’d progressed on a PD-(L)1 and VEGF inhibitor.

Post-PD-(L)1

One question is whether the agency might be similarly lenient when it comes to Litespark-011, but on Merck’s side is the fact that the trial enrolled patients who’d progressed on a PD-(L)1 inhibitor. The study compares Welireg plus Merck and Eisai's Lenvima, versus Cabometyx, and had once been expected to complete in December 2024.

Tuesday’s news bucks the trend of Lenvima failures. Indeed, it had looked like Merck was moving away from Lenvima and towards Exelixis’s zanzalintinib, that group’s Cabometyx follow-on, after a clinical trial collaboration signed last year.

However, the promised phase 3 trials of Welireg plus zanzalintinib still haven’t materialised; Exelixis has said they could start “towards the end of 2025”. But there are still big questions about whether zanzalintinib is safer than Cabometyx, as hoped.

Adjuvant and first line

Meanwhile, in adjuvant renal cancer, the Litespark-022 trial found a benefit on disease-free survival with Welireg plus Keytruda, versus Keytruda alone. Here, overall survival is a secondary endpoint that the trial will continue to assess.

As with Litespark-011, Merck said it would discuss the data with regulators, and present them at an upcoming meeting.

Another phase 3 trial of Welireg could read out next year: Litespark-012 is testing a Welireg/Keytruda/Lenvima triplet in first-line disease, versus Keytruda plus Lenvima, with or without the anti-CTLA-4 MAb quavonlimab.

Welireg sold $509m in 2024, so Merck will need the latest wins to translate into approvals if it’s to meet its blockbuster prediction. If it does, the $1bn it paid for the drug’s developer, Peloton, could look like a good move.

Phase 3 studies of Welireg in renal cell carcinoma

Source: OncologyPipeline.