Arrowhead moves to close the gap with Merck’s Peloton

Arrowhead has tried to bounce back after a tough time on the markets on Friday, revealing the first data on a rival to a Merck & Co project bought for $1.05bn. Arrowhead’s ARO-HIF2 is an RNAi therapy against HIF-2α, and this morning the group said a dose-finding phase 1 study was showing early signs of efficacy. Among 17 third-line or later clear cell renal cell carcinoma (RCC) subjects there has been one partial remission at dose level two, with a third dose now enrolling. Seven of nine evaluable patients have shown HIF-2α reductions of -9% to -82%; the mean of these reductions was -48%. Meanwhile, Merck’s belzutifan appears to be the industry’s only other clinical-stage HIF-2α inhibitor, having been acquired in the group’s $1.05bn purchase of Peloton. Belzutifan has been filed, with a September 15 action date, for front-line Von Hippel-Lindau disease-associated RCC on the basis of a 36% overall remission rate in a phase 2 trial, and an update at this year’s Asco showed the ORR rising to an impressive 49%. Arrowhead is clearly lagging behind, but its early data show ARO-HIF2 doing what it is supposed to, with room to be dosed higher.

Selected HIF-2α inhibitors
Project Company Status Comment
Belzutifan Merck & Co (ex Peloton) Filed for 1L Von Hippel-Lindau disease-associated RCC 30/61 PR; also 22% ORR in relapsed RCC in combo with Cabometyx
ARO-HIF2 Arrowhead Phase 1 1/17 PR in ≥3L RCC
AB521 Arcus Clinical trials to start H2 2021 Part of series said to be potent with favourable pharmacokinetics
SDGR4 Schrödinger Discovery Part of discovery collaboration with Bristol Myers Squibb
Source: Evaluate Pharma & company information.
Efficacy data for Merck's belzutifan in front-line Von Hippel-Lindau disease-associated RCC. Source: Dr Ramaprasad Srinivasan & Asco.

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