Pooled data from three Phase III studies of inclisiran shows durable repsonse in hyperlipidemia.- Novartis

Novartis announced results from a prespecified analysis of pooled data from three Phase III studies evaluating the safety and efficacy of inclisiran, its first-in-class investigational treatment for hyperlipidemia in adults. The pooled analysis of the ORION-9, -10 and -11 Phase III trials showed a durable and potent reduction in LDL-C of 51% when used in addition to other lipid-lowering therapies (LLT) over 17 months of treatment. The prespecified analysis of pooled data is consistent with the efficacy and safety findings of the individual Phase III trial results recently published in The New England Journal of Medicine. Additionally, a prespecified exploratory analysis using the safety reporting from all three trials indicated fewer MACE with inclisiran compared to placebo (7.1%, 9.4% respectively). The overall safety and tolerability profile was generally similar between the inclisiran and placebo groups. While these preliminary observations are based on a low number of events, they are consistent with the general concept that however LDL-C is lowered, it is thought to result in reduced risk of future cardiovascular events. This further supports the research currently underway in the Phase III ORION-4 trial. The ORION-4 trial aims to recruit 15,000 participants – from 150 sites in the United States and the United Kingdom – with pre-existing atherosclerotic cardiovascular disease (ASCVD) and who are unable to achieve LDL-C goal. Expected to finish in 2024, this trial will bring additional information on inclisiran’s effects on cardiovascular outcomes. The data was presented during a Late Breaker session at the American College of Cardiology’s Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC Virtual).Comment: Inclisiran is currently under review by the the FDA and EMA for use in adults with ASCVD or heterozygous familial hypercholesterolemia (HeFH) who have elevated LDL-C while being on a maximum tolerated dose of a LLT. Inclisiran is administered subcutaneously with an initial dose, again at 3 months and then every 6 months, offering a unique dosing regimen. If approved, inclisiran will be the first and only LDL-C-lowering treatment in the siRNA class.