ORION-10: Safety and Efficacy of Inclisiran in Patients with ASCVD and Elevated LDL-C

The use of inclisiran reduces low-density lipoprotein (LDL-C) levels in patients with atherosclerotic cardiovascular disease (ASCVD), new study results presented at the American Heart Association 2019 Scientific Sessions suggest.

For this Phase 3 study, researchers randomized 1,561 patients 18 years of age and older December 2017 and September 2019. The subjects were randomized 1:1 to receive either 300 mg of inclisiran or a placebo, at Day 1, Day 90, Day 270 and Day 450. Subsequently, each subject attended 8 study visits over the duration of 18 months to evaluate the safety and tolerability of inclisiran.

The two primary endpoints of this study were stipulated as the percent change from baseline in LDL-C at Day 510, and the time-adjusted average percentage change from baseline in LDL-C between Day 90 up to Day 540. The study’s secondary endpoints were specified as the mean absolute change in LDL-C at Day 510, the average absolute reduction in LDL-C between Day 90 up to Day 540, and changes in other lipids and lipoproteins.

According to the results of the study, inclisiran dosed initially, again at three months and then every six months thereafter caused placebo-adjusted LDL-C reductions of 58% at day 510 while demonstrating time-averaged placebo-adjusted LDL-C reductions of 56% from days 90 through 540. Moreover, the findings demonstrated inclisiran’s favorable safety profile, with an overall adverse event profile similar to placebo. The researchers observed no treatment-related liver or kidney laboratory test abnormalities.

“Inclisiran achieved durable and potent LDL-C reduction with twice yearly injection in ASCVD patients on appropriate lipid lowering therapies over 18 months of follow-up with a safety profile similar to placebo in a high risk CV population,” the study presentation concluded. “Assuming FDA approval, twice yearly administration coincides with typical twice yearly patient visits with health care providers. Inclisiran therefore potentially offers a novel new treatment for LDL-C.”