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). We expect to release top-line data in the third quarter of 2019, to file a new drug application (NDA) with the FDA in the U.S. in the fourth quarter of 2019, and to file a marketing authorization application (MAA) in Europe in the first quarter of 2020. In these clinical trials, people receive inclisiran or placebo on Day 1 and Day 90, then an additional two doses six months apart.
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
|Trial||Study Purpose / Population||Clinical Phase|
|ORION-10||Atherosclerotic cardiovascular disease (ASCVD) - U.S.||3|
|ORION-11||ASCVD and risk-equivalents - Europe||3|
|ORION-9||Heterozygous familial hypercholesterolemia (HeFH) - Global||3|
|ORION-4||Cardiovascular outcomes trial (CVOT) / ASCVD – United Kingdom and U.S.||3|
|ORION-5||Homozygous familial hypercholesterolemia (HoFH) - Global||3|
|ORION-8||Extension study of ORION-9, -10 and -11/ASCVD – Global||3|
|ORION-3||Long-term extension study of ORION-1 - Global||2|
|Hepatic impairment - U.S.||1|
|TQTc - U.S.||1|
|ORION-11||ASCVD - Global||2 (Completed)|
|ORION-2||Pilot study / Homozygous familial hypercholesterolemia (HoFH) - Global||2 (Completed)|
|ORION-7||Renal impairment - New Zealand||1 (Completed)|