Arrowhead shoots after hypoxia


Merck & Co’s $1.05bn takeover of Peloton Therapeutics last year focused on a new mechanism targeting tumour hypoxia, and now Arrowhead has got in on the game by starting a phase Ib study. Arrowhead's ARO-HIF2 is an RNAi project that targets the transcription factor HIF-2α, which is involved in regulating the body’s response to low oxygen, now being tested in renal cell carcinoma. Peloton’s PT2977, now called MK-6482, was the first project to hit HIF-2α, and Merck paid up handsomely. MK-6482 has oral administration advantages, as ARO-HIF2 will be given by intravenous infusion, and Merck’s project has shown promising early data; a phase III study is under way, also in kidney cancer, versus Afinitor. Checkpoint inhibitors are becoming dominant in renal cancer, and combination strategies could move HIF-2α inhibitors into earlier lines of therapy.

Targeting HIF-2α, the clinical trials so far
Project Company Clinical trial Details Data?
Merck & Co (ex Peloton) MK-6482-005 Phase III, vs Afinitor, n=736 Primary completion 2025
NCT03401788 Ph II in von Hippel -Lindau disease-associated renal cell cancer, n=61 28% ORR
NCT03634540 Ph II Cabometyx combo, n=188 Primary completion 2023
NCT02974738 Ph I, n=125 Early data in 55 patients showed 24% ORR
ARO-HIF2 Arrowhead AROHIF21001  Phase Ib dose-finding study in up to 18 patients Primary completion 2022
Sources: EvaluatePharma,, company releases.

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