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Results of ORION-9 reveal inclisiran has the potential to treat familial hypercholesterolemia with twice-a-year injections.
Results of the phase 3 ORION-9 trial are suggesting inclisiran could be used as an effective therapy for the treatment of heterozygous familial hypercholesterolemia.
In the 18-month trial, which was presented at the American Heart Association (AHA) 2019 Scientific Sessions in Philadelphia, revealed inclisiran met all primary and secondary endpoints, including 50% observed LDL-C lowering at day 510 and the reduction of LDL-C independent of underlying familial hypercholesterolemia genotype.
The phase 3 trial was designed as a double-blind, randomized, placebo-controlled trial to establish the efficacy and safety profile of inclisiran, which was found to reduce LDL-C by 58% compared to placebo in ORION-10. The multicenter trial was conducted across 46 sites in 8 countries and included a cohort of 482 subjects who were randomized 1:1 to 300 mg inclisiran or placebo.
For inclusion in the study, patients needed to be at least 18 years of age, have an LDL-C of 100 mg/dL or greater, be stable on a low-fat diet, using maximally tolerated statin doses. Patients were excluded if they had a major cardiovascular event within 3 months of randomization, had uncontrolled severe hypertension, or had a fasting triglyceride level greater than 400 mg/mL among others.
Primary efficacy endpoints for the study were the percent change in LDL-C compared with placebo at day 510 and the average over days 90 to 540. Secondary endpoints included LDL-C change over time and changes in PCSK9 and other lipids.
Patients were administered therapy on day 1, day 90, day 270, and day 450. Additional follow-up visits were performed at day 30, day 150, day 330, day 510, and day 540.
Upon analyses, investigators observed inclisiran use results in placebo-adjusted LDL-C reductions of 50% at day 510 and time-averaged placebo-adjusted LDL-C reductions of 46% from day 90 through day 540. In regard to the safety profile, the safety profile was similar to placebo except when considering adverse events at the injection site, which occurred in 9% of inclisiran patients and 0 patients in the placebo group.
For more on the results of ORION-9 and what inclisiran could provide to a patient population in need of treatments, MD Magazine® sat down with lead investigator and presenter Frederick Raal, MD, PhD, between sessions at AHA 2019.