Twice yearly administration of PCSK9 siRNA yields persistent LDL-c lowering
Interim results from the ongoing ORION-3 open-label extension study (Group 1, n=290) have now been published, which showed that twice-a-year dosing with inclisiran sodium 300 mg resulted in consistent lowering of LDL-C by more than 50% with overall follow-up of up to three years. Inclisiran was well tolerated, and no material safety issues were observed in the study. These results were presented during a late-breaking clinical trial session at the National Lipid Association (NLA) Scientific Sessions in Miami.
Inclisiran, the first cholesterol-lowering therapy in the siRNA class, is in Phase 3 clinical development to evaluate its ability to lower LDL-C through twice-a-year dosing. Pivotal Phase 3 readouts for inclisiran are expected in the third quarter. ORION-3 (n=382) is an open-label extension study of the Phase 2 ORION-1 trial to assess the efficacy, safety and tolerability of long-term dosing of inclisiran.
In this interim analysis of ORION-3, inclisiran demonstrated a 51% (64.0 mg/dL, p<0.001) reduction in LDL-C levels through day 210, which was the study’s primary endpoint. The time-averaged absolute LDL-C reduction with inclisiran was 59.4 mg/dL (p<0.001). These effects were independent of dose level and number of doses of inclisiran previously given in the ORION-1 study.
With overall follow-up of approximately three years from the first dose in ORION-1, no change in the overall safety profile was observed in this interim analysis of ORION-3 compared to the one-year follow-up in ORION-1. Inclisiran was well tolerated and no material safety issues were observed, including no elevations of liver enzymes or changes in renal function considered related to study medication. Clinically relevant injection site reactions were infrequent, mild or moderate, and transient, in line with observations in ORION-1.
More than 3,000 patient-years of inclisiran safety data have been accumulated to date in the ORION program. The data from ORION-3, as well as ongoing review of blinded data to date from the Phase 3 trials, show no material safety issues; data are at least as favorable as those generated and published from the ORION-1 Phase 2 trial.