Final Clinical Results from ORION-1 Phase 2 Study of Inclisiran, in Development for Hypercholesterolemia
Alnylam and The Medicines Company reported final results from the ORION-1 Phase 2 study of inclisiran, an investigational RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia, at the American College of Cardiology (ACC) Scientific Session 2017 in Washington DC.
Results (N=497 3:1, inclisiran:placebo) showed that administration of inclisiran (300 mg at Day-1 and Day-90) resulted in clamped PCSK9 knockdown and robust, sustained lowering of LDL-C by an average of 52.6% and up to 80.9% at Day-180, with a time-adjusted mean of greater than 50% through Day-270. Importantly, every patient in this dose cohort (N=61) responded with significant LDL-C lowering. These results are supportive of an optimal dosing regimen of two 300 mg doses administered on Day-1 and Day-90, followed by 300mg dosing every six months thereafter.
Inclisiran was well tolerated with no material safety issues observed, including no drug-related elevations of liver enzymes. The overall incidence of treatment emergent adverse events was similar in both patients randomized to placebo and patients randomized to inclisiran, with no significant difference between inclisiran doses. Injection site reactions were observed in 5.1% of patients, and all were mild or moderate and transient. There were no clinically significant changes in liver function tests, renal function tests, or hematologic parameters, including platelets.
Inclisiran is a first-in-class PCSK9 synthesis inhibitor with the potential for a highly competitive profile as compared with anti-PCSK9 monoclonal antibodies. Inclisiran represents a potentially transformative treatment option for patients with hypercholesterolemia, and we look forward to its continued advancement into Phase 3 studies by our partners at The Medicines Company.