Low-dose Inclisiran Linked with Reduced LDL Cholesterol

A infrequent dosing regimen of inclisiran could offer another therapeutic option for lowering low-density lipoprotein cholesterol (LDL-C).

The prespecified analysis and one-year follow up of the ORION-1 randomized, double-blind, placebo-controlled multicenter phase 2 clinical trial was published in JAMA Cardiology explored whether inclisiran would reduce mean LDL-C exposure, aimed at us in patients who had trouble adhering to LDL-C-lowering medications that require more frequent administration. The study included 501 participants (65% men) with elevated LDL-C levels who received either one dose (100 mg, 200 mg, and 300 mg doses on day one), two doses (100 mg, 200 mg, or 300 mg on days 1 and 90), or placebo. Participants were followed-up monthly for LDL-C and PCSK9 measurements. Participants were also taking maximally tolerated statin therapy. The primary outcomes of interest was the duration of time to return to within 20% change from baseline for LDL-C levels, and also time-averaged LDL-C reductions over one year.

According to the study results, baseline LDL-C was 128 mg/dL among the 501 randomized participants. The percentage of participants who followed up to day 360 due to LDL-C not returning to within 20% of change from baseline ranged from 48.3% to 65% in the single dose arm and from 55.9% to 83.1% in the two-dose arm. The authors reported that the time-averaged reduction in LDL-C over one year after the single-dose regimen was between 29.5% and 38.7% (P<0.001 between groups) and between 29.9% and 46.4% (P<0.001 between groups). Notably, the double-dose, 300 mg regimen was associated with the highest proportion of responders at day 360 and the largest mean reduction in LDL-C over one year. Adverse events were reported to be similar in between all study groups.

“Treatment with inclisiran resulted in durable reductions in LDL-C over 1 year, [and] inclisiran may offer a novel approach to LDL-C reduction with the convenience of infrequent dosing,” the researchers wrote of the findings. “Through potent and durable lowering of LDL-C with a twice-a-year dosing regimen, inclisiran could offer a sustained lipid-lowering therapeutic option in the future.”