Heterozygous LDLR gene mutations were most prevalent when screening for autosomal dominant hypercholesterolemia in hypercholesterolemia patients and relatives from Norway.

This pooled patient-level analysis of three phase 3 trials (ORION-9, -10 and -11) shows that inclisiran reduces LDL-c on average by 50.7% compared to placebo in patients on maximally tolerated statin-therapy.

The ODYSSEY APPRISE study showed in general good tolerability for alirocumab in high CV risk patients and ~50% reduction in LDL-c after 12 weeks of alirocumab treatment.

The PCSK9 inhibitor alirocumab has been approved by the US Food and Drug Administration (FDA) as an adjunct to other LDL-c lowering therapies for the treatment of adult patients with homozygous familial hypercholesterolemia.

Patients with LDLR and PCSK9 gene variants had higher levels of LDL-c and more frequent occurrence of nonfatal MI than those with single LDLR variants. This was especially observed in men.

The FDA approved the ANGPTL3 inhibitor evinacumab for the treatment of patients with homozygous familial hypercholesterolemia (HoFH) to lower LDL-c.

This phase 2 trial showed that ANGPTL3 inhibition by evinacumab significantly reduced LDL-c by ~50% at maximum dose in patients with refractory hypercholesterolemia.

Inclisiran has received approval from the European Commission (EC) for the treatment of adult patients with atherosclerotic CVD (ASCVD), ASCVD-risk equivalent and heterozygous FH.

Following the results from the ORION program, the CHMP of EMA has issued a positive opinion on inclisiran to reduce LDL-c in patients with hypercholesterolemia or mixed dyslipidemia.

EAS 2020 Inhibition of ANGPTL3 with evinacumab reduced LDL-c levels significantly in HoFH patients with little to no LDL receptor function.

EAS 2020 A post-hoc analysis of the ELIPSE HoFH trial in patients with little to no LDL receptor activity demonstrated a large reduction of LDL-c with the ANGPTL3 inhibitor evinacumab compared to placebo.

EAS 2020 A subanalysis of ORION-9 showed that lowering of LDL-c by inclisiran was similar across subgroups of genotypes in those with heterozygous FH.