Clinical Development

ORION clinical development program

At The Medicines Company, we are devoted to the development of inclisiran – a small interfering RNA (siRNA) therapy being studied to evaluate its ability to lower low-density lipoprotein (LDL) cholesterol – also known as LDL-C or bad cholesterol. Inclisiran is designed to prevent the production of proprotein convertase subtilisin/kexin type 9 (PCSK9) at its primary source in the liver. Inclisiran is not yet approved for use by the FDA or any other regulatory authority.

The ORION program includes pivotal Phase 3 trials (ORION-9, ORION-10 and ORION-11), designed to evaluate the safety and efficacy of inclisiran in people with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C despite the maximum tolerated dose of LDL-C-lowering therapies, as well as individuals with familial hypercholesterolemia (FH). In these clinical trials, people receive inclisiran or placebo on day one, again at day 90 (three months), then every six months thereafter for a total of four doses over the respective studies’ duration.

The company presented efficacy, tolerability and safety data from ORION-11 during a late-breaking session at the European Society of Cardiology’s ESC Congress 2019 in Paris. In late September, the company announced positive top-line results for both ORION-9 and ORION-10 and will share full results from these studies in November at the American Heart Association Scientific Sessions in Philadelphia. Regulatory submissions for inclisiran are anticipated to occur in the U.S. in the fourth quarter of 2019 and in Europe in the first quarter of 2020.

Study participants who have completed their respective Phase 3 studies are now enrolling into ORION-8, an open-label, long-term extension study in which patients completing ORION-5, ORION-9, ORION-10 and ORION-11 will receive inclisiran for up to three years to generate longer-term efficacy, safety and tolerability data.

In addition to these studies, the ORION-4 trial, which began enrolling in October 2018, is designed to evaluate cardiovascular outcomes in 15,000 people being treated with inclisiran or placebo.

ORION clinical trials

TrialStudy Purpose / PopulationClinical Phase
ORION-10Atherosclerotic cardiovascular disease (ASCVD) - U.S.3 (Completed)
ORION-11ASCVD and risk-equivalents - Europe3 (Completed)
ORION-9Heterozygous familial hypercholesterolemia (HeFH) - Global3 (Completed)
ORION-4Cardiovascular outcomes trial (CVOT) / ASCVD – United Kingdom and U.S.3
ORION-5Homozygous familial hypercholesterolemia (HoFH) - Global3
ORION-8Extension study of ORION-9, -10 and -11/ASCVD – Global3
ORION-32Long-term extension study of ORION-1 - Global2
Hepatic impairment - U.S.1 (Completed)
TQTc - U.S.1 (Completed)
ORION-11ASCVD - Global2 (Completed)
ORION-2Pilot study / Homozygous familial hypercholesterolemia (HoFH) - Global2 (Completed)
ORION-7Renal impairment - New Zealand1 (Completed)
1 Results from ORION-1 were presented at the American College of Cardiology’s 66th Annual Scientific Session and published in The New England Journal of Medicine.2 Interim results from ORION-3 for Group 1 only (subjects previously treated with any inclisiran sodium dose in ORION-1) were presented at the 2019 National Lipid Association (NLA) Scientific Sessions. See the news release for more information.

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