A prespecified exploratory analysis using the safety data from the 3 trials indicated fewer major adverse cardiovascular events (MACE) with inclisiran compared with placebo.
Results from an analysis of pooled data from 3 phase 3 studies evaluating the safety and efficacy of inclisiran for treating hyperlipidemia in adults showed a durable, potent reduction in low-density lipoprotein cholesterol (LDL-C) of 51% when used in addition to other lipid-lowering therapies over 17 months of treatment, according to a Novartis press release.
In addition, a prespecified exploratory analysis using the safety data from the 3 trials indicated fewer major adverse cardiovascular events (MACE) with inclisiran compared with placebo. The trials showed that the overall safety and tolerability profile was generally similar between inclisiran and placebo groups.
The preliminary observations are consistent with the general concept that however LDL-C is lowered, it is thought to result in a reduced risk of future cardiovascular events.
Further research is underway in the phase 3 ORION-4 trial, which aims to recruit 15,000 participants from 150 sites in the United States and the United Kingdom who have pre-existing atherosclerotic cardiovascular disease (ASCVD) and are unable to achieve LDL-C goals. This trial, which is intended to provide additional information on inclisiran’s effects on cardiovascular outcomes, is expected to finish in 2024.
The pooled analysis includes data from the ORION-9, -10, and -11 trials evaluating inclisiran in patients with heterozygous familial hypercholesterolemia, ASCVD, and ASCVD risk equivalents. The primary endpoints were achieved in all 3 studies, and each analysis assessed inclisiran’s efficacy for lowering of LDL-C and other lipids/lipoproteins, as well as safety and tolerability.
Inclisiran resulted in placebo-adjusted LDL-C reduction at 17 months of 51% and a time-adjusted placebo-adjusted percentage reduction in LDL-C between 3 and 18 months of 51%. In the prespecified exploratory safety analysis, MACE were significantly lower with inclisiran versus placebo, including non-fatal myocardial infarction, stroke, cardiovascular death, and resuscitated cardiac arrest. Overall, the safety and tolerability profile were generally similar between the inclisiran and placebo groups, and no differences were seen in adverse outcomes between the groups observed.
Inclisiran is under review by the FDA for use in adults with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who have elevated LDL-C while being on a maximum tolerated dose of a lipid-lowering therapy. Inclisiran is administered subcutaneously with an initial dose, again at 3 months, and then every 6 months. If approved, it will be the first and only LDL-C-lowering treatment in the siRNA class.
Novartis new analysis further showed durable and potent LDL-C reduction with inclisiran, an investigational first-in-class siRNA cholesterol-lowering treatment [news release]. East Hanover, NJ; PR Newswire: March 28, 2020. https://www.prnewswire.com/news-releases/novartis-new-analysis-further-showed-durable-and-potent-ldl-c-reduction-with-inclisiran-an-investigational-first-in-class-sirna-cholesterol-lowering-treatment-301031312.html. Accessed March 30, 2020.