Topline ORION-11: Inclisiran Scores on All End Points

Patrice Wendling

August 26, 2019

The phase 3 ORION-11 study of inclisiran sodium met all primary and secondary end points, with efficacy consistent with findings from phase 1 and 2 studies, The Medicines Company announced today

ORION-11 is the first of three pivotal phase 3 studies of the investigational small interfering (si)RNA therapy, which lowers low-density-lipoprotein cholesterol (LDL-C) using RNA interference to inhibit proprotein convertase subtilisin kexin type9 (PCSK9) synthesis. As previously reported, inclisiran injection, at various doses, led to a mean reduction in LDL-C of up to 41.9% at day 180 in the phase 2 ORION-1 study.

ORION-11 enrolled 1617 patients with atherosclerotic cardiovascular disease (ASCVD), or ASCVD-risk equivalents, and elevated LDL-C despite maximally tolerated statins. Patients received subcutaneous inclisiran 300 mg at baseline, at 3 months, and then every 6 months thereafter.

The primary end points were percentage change in LDL-C from baseline to 17 months and time-adjusted percentage change in LDL-C from baseline after 3 months and up to 18 months. Key secondary end points included the mean absolute change at 17 months, the average absolute reduction from 3 months up to 18 months, and changes in other lipids and lipoproteins.

The trial showed that inclisiran is well tolerated and confirmed that the safety profile is at least as favorable as that in the ORION-1 and ORION-3 open-label extension studies, according to the company.

A full report will be presented 8:30 CET Monday, September 2 during a late-breaking science session at the European Society of Cardiology (ESC) Congress in Paris, and will be covered by | Medscape Cardiology.

Additional phase 3 data from the ORION-9 and ORION-10 studies are expected to be reported later in the third quarter in advance of approval applications to the US Food and Drug Administration in the fourth quarter of 2019 and to the European Medicines Agency in the first quarter of 2020, the company said.

Follow Patrice Wendling on Twitter: @pwendl. For more from | Medscape Cardiology, join us on Twitter and Facebook.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: