Merck hints at progress beyond Welireg’s approved niche
It was late-line kidney cancer data with the molecule that would become Welireg that persuaded Merck & Co to pay over $1bn to acquire Peloton Therapeutics, and now this indication could invigorate sales of the drug. Today the phase 3 Litespark-005 study was toplined positive for PFS, though its co-primary OS endpoint failed to hit significance. It is unclear what the bar was for OS at this interim analysis, so investors have to hope that sufficient alpha allocation remains for OS to hit at a subsequent readout. Welireg, the first approved HIF-2α inhibitor, sold $123m last year in its niche indication of Von Hippel-Lindau disease-associated renal cancer, but needs to win in bigger settings to justify the Peloton acquisition price. Among rival HIF-2α projects Arcus is developing AB521, but Arrowhead discontinued ARO-HIF2, an RNAi asset, last year. Litespark-005 tested Welireg in third-line renal cell carcinoma against everolimus, and Merck plans to move the drug up the treatment ladder into front-line and adjuvant uses. The group expects Welireg to become a blockbuster in the medium term, and Litespeed-005 marks a cautious step towards this goal.
Merck’s plan to expand Welireg’s target market
| Trial | Renal cancer setting | Outcome |
|---|---|---|
| Litespark-004* | Von Hippel Lindau disease-associated, single-cohort monotherapy | Approved on the basis of 49% ORR |
| Litespark-005 | 2nd/3rd-line (post PD-(L)1 MAb + VEGF inhibitor, given sequentially or in combination) monotherapy, vs everolimus | Positive for PFS, negative for OS at interim analysis |
| Litespark-011 | 2nd-line Lenvima combo, vs Cabometyx | Ends Dec 2024 |
| Litespark-012 | 1st-line Keytruda + Lenvima combo, vs Keytruda + Lenvima** | Ends Oct 2026 |
| Litespark-022 | Adjuvant Keytruda combo, vs Keytruda | Ends Oct 2027 |
Note: updated to clarify the Litespark-005 setting; *phase 2, all others are phase 3; **also tests a Keytruda + quavonlimab + Lenvima cohort.
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