The Medicines Company announced detailed results from ORION-10, the second of three pivotal 18-month low-density lipoprotein cholesterol (LDL-C) lowering Phase 3 clinical studies of inclisiran, an investigational twice-yearly therapy to reduce LDL-C and the first and only cholesterol-lowering treatment in the siRNA (small-interfering RNA) class.
In ORION-10, twice-yearly dosing with inclisiran sodium 300 mg met all primary and secondary efficacy endpoints, was well-tolerated and again demonstrated an excellent safety profile. Full study results were presented during a late-breaking science session at the American Heart Association (AHA) Scientific Sessions in Philadelphia.
“Cumulative exposure to high LDL-C levels presents a significant risk of future heart attacks and strokes for millions of people, particularly those with ASCVD,” said study principal investigator R. Scott Wright, M.D., Professor of Medicine, Consultant in Cardiology, Mayo Clinic in Rochester, Minnesota. “The data from ORION-10 show that inclisiran lowers LDL-C significantly and sustains reductions over a six-month period with a safety profile similar to placebo.”
For the primary endpoints of ORION-10, inclisiran delivered placebo-adjusted LDL-C reductions of 58% (p<0.0001) at day 510 and demonstrated time-averaged placebo-adjusted LDL-C reductions of 56% (p<0.0001) from days 90 through 540.
The overall adverse event profiles of the placebo- and inclisiran-treated groups in ORION-10 were similar. A similar proportion of patients in the placebo and inclisiran groups experienced at least one serious treatment emergent adverse event (26.3% vs. 22.4%). The incidences of deaths (1.4% vs. 1.5%) and malignancies (3.3% vs. 3.3%) were also comparable between the placebo and inclisiran groups, respectively.
Clinically significant elevations in liver function tests (ALT 0.3% vs. 0.3%, AST 0.6% vs. 0.5%) and serum creatinine increases (3.9% vs. 3.9%) were similar between the placebo and inclisiran groups, respectively. Clinically relevant adverse events at the injection site, predominantly mild and always transient, were reported in 0.9% of placebo-treated patients vs. 2.6% of inclisiran-treated patients.
“The results from ORION-10 are outstanding and provide yet another confirmation of the highly differentiated clinical profile of inclisiran,” said Mark Timney, Chief Executive Officer of The Medicines Company. “We believe that inclisiran is ideally suited to address the effects of cumulative exposure to LDL-C and has the potential to change the course of how healthcare professionals manage ASCVD risk for the millions of patients who struggle to reach their LDL-C goals.”
ORION-10 data will be submitted to a peer-reviewed medical journal. The company expects to file regulatory submissions in the U.S. in the fourth quarter of 2019 and in Europe in the first quarter of 2020.
Data from ORION-9, a Phase 3 clinical study of inclisiran in patients with heterozygous familial hypercholesterolemia (HeFH), will be presented at AHA on Monday, November 18, 9:24am EST, during Late Breaking Science VI: New Frontiers in Lipid Therapy. The company previously announced (click here) topline results of ORION-9.
Source: Company Press Release