Regeneron’s Evkeeza leads a new class of lipid lowerers


Homozygous familial hypercholesterolaemia affects just 1,300 US patients, but this has not stopped Regeneron pushing on with a novel therapy to treat the disorder. Neither has it stopped others following in Regeneron’s wake. Regeneron got the FDA nod on Friday for Evkeeza, an antibody against ANGPTL3, a protein involved in lipid metabolism. Other ANGPTL3-targeting contenders are some way behind, with the most advanced being Ionis/Pfizer’s antisense project vupanorsen, which began phase IIb late last year. Both vupanorsen and Arrowhead’s RNAi asset ARO-ANG3 are subcutaneous, possibly giving them an edge over Evkeeza, which is given intravenously every four weeks. Still, Regeneron now has the chance to corner the market, although this might not amount to much, with Evercore ISI analysts putting the opportunity at $200-400m per year. Regeneron looks like it plans to make every patient count: Evkeeza's price will be weight based, but the company estimates its average list price will be $450,000 per year. This means that the antibody could be reserved for the most severe patients or those who have failed other lipid-lowering drugs.

ANGPTL3 inhibitors in development for cardiometabolic indications
Project Company Description Indication  Trial details
Evkeeza (evinacumab) Regeneron Anti-ANGPTL3 MAb HoFH Elipse (NCT03399786), 49-point reduction in LDL-C vs SOC 
Phase II
Vupanorsen (AKCEA-ANGPTL3-LRx/ PF-07285557) Ionis/Pfizer ANGPTL3 antisense oligonucleotide Dyslipidaemias Translate Timi 70 (NCT04516291), completes Oct 2021
Phase I 
ARO-ANG3 Arrowhead Anti-ANGPTL3 RNAi therapeutic Dyslipidaemias NCT03747224, completes May 2021
ANGPTL3/8 antibody Lilly Anti-ANGPTL3/8 antibody Diabetes -
ANGPTL3-siRNA Lilly Anti-ANGPTL3 small interfering RNA Diabetes -
HoFH: homozygous familial hypercholesterolaemia. Source: EvaluatePharma &

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