Inclisiran is a drug that reduces the amount of LDL-C in the bloodstream by improving the liver's natural ability to prevent the production of a protein that plays a role in keeping circulating cholesterol levels high. High cholesterol is a serious health issue that needs to be managed immediately, several medications to prevent cholesterol levels in blood are presently available in market.
A trial ORION-4 in ClinicalTrials.gov reported that compared to the other LDL-C-lowering medications, such as statins, ezetimibe and PCSK-9 inhibitors, inclisiran proposes an infrequent dosing of twice a year, while simultaneously providing a significant reduction of LDL-C.
Statins and ezetimibe require daily dosing, while PCSK9 inhibitors are administered every 2 or 4 weeks. The poor adherence to statins is associated with significant increases in total mortality, as well as cardiovascular morbidity and mortality.
Investigated the effects of inclisiran on major adverse cardiovascular events. Approximately 15,000 participants aged 55 years or older with pre-existing atherosclerotic cardiovascular disease were randomized between inclisiran sodium 300 mg and matching placebo (given by subcutaneous injection on the day of randomization, at 3 months and then every 6-months) in a 1:1 ratio for a planned median duration of about 5 years.
The primary outcome of ORION-4 is defined as time to first occurrence of coronary heart disease (CHD) death, myocardial infarction (MI), fatal or non-fatal ischemic stroke, or urgent coronary revascularization procedure. The secondary outcomes include the number of participants with a composite of CHD death or MI and the number of participants with cardiovascular death.
Its prolonged effect offered an advantage against medication non-compliance, which is one of the main causes for not achieving LDL-C goals with standard therapy. Inclisiran has also proven to have a relatively safe profile with adverse effects occurring in similar frequency as with placebo. The results of the ORION-4 trial provided valuable information regarding the benefit of inclisiran in reducing major adverse cardiovascular events and improving outcomes in patients with ASCVD.
Reference: 10.2147/TCRM.S230592