EASC 2023 – Arrowhead takes on Regeneron in cholesterol lowering

Regeneron’s lipid-lowering antibody Evkeeza has not been a big seller so far, but other groups are still hoping to emulate its mechanism, ANGPTL3 inhibition. And Arrowhead looks like it has got something just as good but more convenient: its RNA interference project ARO-ANG3 is given subcutaneously every quarter, versus Evkeeza’s once-monthly intravenous delivery. Caution is warranted when comparing across trials – especially as the latest data, presented today at the European Atherosclerosis Society Congress, come from an uncontrolled phase 2 study, called Gateway, in just 18 patients with homozygous familial hypercholesterolaemia (HoFH). ARO-ANG3 also looks better than Ionis’s anti-ANGPTL3 antisense asset vupanorsen, which Pfizer abandoned last year on disappointing LDL lowering. HoFH only affects around 1,300 US patients; a spokesperson for Arrowhead told Evaluate Vantage it is focused on this population for now, although it could go broader in future: it has also tested ARO-ANG3 in a broad mixed dyslipidaemia population in the phase 2 Arches-2 trial. Others targeting ANGPTL3 include Lilly, with the Dicerna-originated RNA interference project solbinsiran in phase 2, and Verve Therapeutics, which plans to start clinical trials of its in vivo base editing candidate VERVE-201 in the second half of 2024.

Cross-trial comparison of ANGPTL3 inhibitors in HoFH
Project and trial  ARO-ANG3, Gateway* Evkeeza, ELIPSE-HoFH**
15mg/kg IV q4wk
Dose 200mg SC q12wk 300mg SC q12wk
Reduction in LDL-C 48% 44% 47%
Reduction in ApoB 39% 35% 41%
Note: both studies enrolled pts on other lipid-lowering therapies incl. statins & PCKS9 inhibitors; results not placebo adjusted. *Data at wk 20; **Data at wk 24. Source: EASC poster & product label.

This story has been updated to include comments from Arrowhead on future development plans.

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