Abstract
Inclisiran is a novel drug that inhibits PCSK9 synthesis specifically in the liver, harnessing the natural mechanism of RNAi. Phase I and II data show that inclisiran lowers low-density lipoprotein cholesterol levels on average by >50% with a duration of effect that enables twice-yearly dosing. Phases I, II and emerging Phase III data support inclisiran’s safety, tolerability and risk–benefit profile. The ongoing ORION program includes Phase III trials that will provide robust evidence of inclisiran’s safety and efficacy in individuals at high risk of atherosclerotic cardiovascular disease (ASCVD), including established ASCVD and familial hypercholesterolemia. In addition, the ORION-4 trial will assess the impact of inclisiran on cardiovascular outcomes in approximately 15,000 ASCVD subjects.
Financial & competing interests disclosure
RM Stoekenbroek, PLJ Winjgaard and D Kallend are employees of The Medicines Company. JJP Katelein reports personal fees from Sanofi, Affiris, Amgen, Akarna, Astra Zeneca, Catabasis, Cerenis, Corvidia, CSL-Behring, Cymabay, Esperion, Gemphire, Ionis, Kowa, Madrigal, Novartis, Eli Lilly, Pfizer, Regeneron, Roche and Sanofi outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.