Compiling data from 7 clinical trials, researchers conclude that the small interfering RNA (siRNA) agent inclisiran was well tolerated during long-term treatment of dyslipidemias in a diverse population. “Taken together with the effective and consistent LDL-C–lowering ability of inclisiran, these data lend support to its long-term use in patients at high [cardiovascular] risk,” the authors conclude.
The data come from completed (ORION-1, -3, -5, -9, -10, and -11) and ongoing (ORION-8) trials of patients treated with inclisiran sodium 300 mg or placebo. This post hoc analysis considers exposure-adjusted incidence rates and Kaplan-Meier estimates of cumulative incidence of reported treatment-emergent adverse events (TEAE), abnormal laboratory measurements, and incidence of antidrug antibodies.
“This analysis included 3,576 patients treated with inclisiran for up to 6 years and 1,968 patients treated with placebo for up to 1.5 years, with 9,982.1 and 2,647.7 patient-years of exposure, respectively,” the authors write. “Baseline characteristics were balanced between groups. Kaplan-Meier analyses showed that TEAEs that were serious or led to discontinuation; hepatic, muscle, and kidney events; incident diabetes; and elevations of creatine kinase or creatinine accrued at a comparable rate between groups for up to 1.5 years, with similar trends continuing for inclisiran beyond this period. Numerically fewer major cardiovascular events reported as TEAEs occurred with inclisiran during this period. Treatment-induced antidrug antibodies were uncommon with inclisiran (4.6%), with few of these persistent (1.4%) and not associated with greater incidence of TEAEs leading to study drug discontinuation or serious TEAEs.”
The current state of evidence on the safety, efficacy, and clinical effectiveness of the siRNA therapies is the focus of an accompanying editorial.