#VisualAbstract: Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia

1. Inclisiran, a small interfering RNA, therapy was shown to significantly lower levels of low-density lipoprotein (LDL) cholesterol compared to the placebo in adults with heterozygous familial hypercholesterolemia.

2. The reduction in LDL cholesterol levels, via inclisiran therapy, was shown to be similar to the reduction achieved with proprotein convertase subtilisin-kexin type 9 (PCSK9) monoclonal antibody therapy.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Current pharmacologic management of familial hypercholesterolemia includes high intensity statins and monoclonal antibodies directed against PCSK9. Both therapies have been shown to reduce LDL cholesterol but require frequent dosing regimens. The ORION-9 trial evaluated inclisiran, a novel small interfering RNA therapeutic that also acts on PCSK9, in a large patient cohort of adults with heterozygous familial hypercholesterolemia who had been treated with a maximally accepted statin therapy dose. The study found a significant decrease in LDL cholesterol from baseline in the inclisiran group compared to the placebo group.

Of note, while the majority of the patients were also taking a statin and ezetimibe, the regimens across participants was not consistent. Furthermore, the combined effects of various statins, ezetimibe, and inclisiran on LDL cholesterol was not separately analyzed. Nonetheless, this study is strengthened by the diagnostic measures used to assess the effect of inclisiran on LDL cholesterol levels. For physicians, these findings provided evidence for another therapy for patients who have failed high intensity statins and do not want frequent dosing regimens.

Click to read the study in NEJM

©2020 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.