The Medicines Company announced positive topline results from the phase 3 ORION-9 and ORION-10 studies for inclisiran in patients with either heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease (ASCVD), respectively, plus elevated low-density lipoprotein cholesterol (LDL-C) despite maximally tolerated statin therapy (with or without ezetimibe).
Inclisiran is a chemically synthesized small interfering RNA (siRNA) that targets proprotein convertase subtilisin-kexin type 9 (PCSK9) messenger RNA. The subcutaneous (SC) injectable is being investigated for its ability to lower LDL-C through twice-a-year dosing.
In the ORION-9 (N=482) and ORION-10 (N=1561) studies, patients were randomized to receive either inclisiran 300mg SC or placebo on Day 1, Day 90, and then every 6 months up to Day 540. The primary end points of both studies were the percentage change in LDL-C from baseline to Day 510 and the time-adjusted percent change in LDL-C from baseline after Day 90 to Day 540.
Results from both studies demonstrated inclisiran to achieve all primary and secondary end points with an efficacy, safety, and tolerability profile similar to that observed in the ORION-11 study. Additionally, there were no treatment-related liver or renal laboratory abnormalities with inclisiran.
Full detailed data from ORION-9 and ORION-10 will be presented at the American Heart Association (AHA) Scientific Sessions in Philadelphia in November 2019.
“The Medicines Company thanks the more than 3600 patients and their dedicated clinical site teams who participated in the Phase 3 LDL-C lowering clinical program for inclisiran,” said Peter Wijngaard, PhD, Chief Development Officer of The Medicines Company. “Seeing such consistent results across the breadth of our clinical development program in patients treated with inclisiran for up to 3 years, including 18 months in pivotal phase 3 studies, is truly impressive.
Patients who have completed their respective phase 3 ORION-9, ORION-10, and ORION-11 studies will be enrolled into an ongoing, open-label, long-term extension study (ORION-8) to investigate the efficacy and safety of inclisiran over the course of 3 years.
The Company plans to submit a New Drug Application with the Food and Drug Administration in the fourth quarter of 2019.
For more information visit themedicinescompany.com.