Inclisiran, a PCSK9 synthesis inhibitor designed to lower cholesterol levels in the blood, was shown to significantly lower low-density lipoprotein cholesterol (LDL-C) while maintaining standards of safety and tolerability for every single patient in a clinical trial, a triumph in treatment for cardiovascular disease caused by high cholesterol.

The much anticipated study, titled ORION-1, was presented March 17 at American College of Cardiology’s 66th Annual Scientific Session. It was also published online today in The New England Journal of Medicine.

The study, a joint project between The Medicines Company in Parsippany-Troy Hill, New Jersey, and Alnylam Pharmaceuticals in Cambridge, Massachusetts, was led by Kausik K. Ray, MD, a professor on the School of Public Health at the Imperial College London.

“There were no safety concerns,” Ray said during his presentation. “If you look at treatment and adverse events, these did not differ between inclisiran and placebo.”

ORION-1 was a randomized, double-blind, placebo-controlled phase 2, multicenter trial. Once the nearly 500 patients received inclisiran doses, results showed that they all experienced constant LDL-C reductions over time and that it was safe for them. The researchers saw no signs of neuropathy, change in renal function or thrombocytopenia. The average age the patients was 63 and about two-thirds of the patients were male.

“The unique dosing regimen virtually eliminates variability in LDL-C levels over time and inclisiran may, therefore, solve one of the most vexing challenges of cardiovascular medicine—namely, how to make sure everyone responds to treatment,” said John J.P. Kastelein, MD, PhD, a professor of medicine and the chairman of the Department of Vascular Medicine at the Academic Medical Center at the University of Amsterdam.

A new trial, ORION-4, has already been initiated. The researchers expect to include cardiovascular outcomes in high-risk primary and secondary prevention patients who have an average baseline of LDL-C of 130 mg/dL.

“The groundbreaking results from ORION-1 are compelling and affirm inclisiran’s unique and highly-differentiated attributes, and its game-changing potential to address the unmet needs of millions of at-risk, often non-adherent, patients worldwide who continue to struggle with high cholesterol given the limitations of available therapies,” said Clive Meanwell, MD, PhD, CEO at the Medicines Company. “We are singularly focused on thoughtfully and aggressively advancing inclisiran into Phase III development.”