Two Phase 3 Trials of Inclisiran in Patients with Elevated L
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Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin–kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing. Thus study concluded that Reductions in LDL cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months. More injection-site adverse events occurred with inclisiran than with placebo.

The author enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial) and patients with atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11 trial) who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose. Patients were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter over a period of 540 days. The coprimary end points in each trial were the placebo-corrected percentage change in LDL cholesterol level from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol level from baseline after day 90 and up to day 540.

Results: A total of 1561 and 1617 patients underwent randomization in the ORION-10 and ORION-11 trials, respectively. Mean LDL cholesterol levels at baseline were 104.7±38.3 mg per deciliter and 105.5±39.1 mg per deciliter, respectively. At day 510, inclisiran reduced LDL cholesterol levels by 52.3% in the ORION-10 trial and by 49.9% in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% and 49.2%. Adverse events were generally similar in the inclisiran and placebo groups in each trial, although injection-site adverse events were more frequent with inclisiran than with placebo; such reactions were generally mild, and none were severe or persistent.

Conclusively, Reductions in LDL cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months. More injection-site adverse events occurred with inclisiran than with placebo.

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1912387?query=featured_home
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