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|
|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, clinicaltrials.gov, company releases.|