28 Aug, 2017 New Positive One-Year Data from ORION-1 Phase 2 Study of Inclisiran, in Development for Hypercholesterolemia
Alnylam and The Medicines Company reported new, one-year data from the ORION-1 Phase 2 study of inclisiran, an investigational RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia, at the European Society of Cardiology (ESC) Congress 2017 in Barcelona, Spain.
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 56% at Day-150 and 51% at Day-180. For the subsequent six-month period – from Day-90 to Day-270 – the time-averaged LDL-C reduction was 51% with minimum intra-patient variability over time (all comparisons to placebo P <0.0001). These data underscore the selection of a six monthly maintenance dose of 300 mg in Phase 3 trials.
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.
Inclisiran is a first-in-class PCSK9 synthesis inhibitor with the potential for a highly competitive profile as compared with anti-PCSK9 monoclonal antibodies. We believe inclisiran represents a potentially transformative treatment option for patients with hypercholesterolemia, and we look forward to the planned initiation of the Phase 3 program by our partners at The Medicines Company.