ORION-13 is the first randomized controlled trial to test inclisiran—a twice-yearly injectable siRNA that silences hepatic PCSK9—in adolescents aged 12–17 with homozygous familial hypercholesterolemia (HoFH). Thirteen patients on maximally tolerated statins were randomized 2:1 to inclisiran 300 mg or placebo for one year. Inclisiran produced a placebo-adjusted 33.3% reduction in LDL-C by day 330, with PCSK9 falling 60.2%. Two-thirds of treated teens achieved greater than 15% LDL-C reduction. No serious adverse events or treatment discontinuations occurred. The findings suggest inclisiran could meaningfully expand treatment options for adolescents with this life-threatening, difficult-to-treat genetic condition.
