# Inclisiran bij adolescenten met homozygote FH: effectiviteit en veiligheid

*geplaatst 2025-06-24 · Cholesterol · Circulation · doi 10.1161/CIRCULATIONAHA.124.073233 · https://hartvaat.nl/2025/06/24/inclisiran-bij-adolescenten-met-homozygote-fh-effectiviteit-en-veiligheid/*

Studie toonde dat inclisiran ook bij adolescenten met homozygote FH effectief en veilig het LDL verlaagt. Vroege behandeling in deze ernstige populatie kan de cardiovasculaire prognose verbeteren.

## English: Efficacy and Safety of Inclisiran in Adolescents With Genetically Confirmed Homozygous Familial Hypercholesterolemia: Results From the Double-Blind, Placebo-Controlled Part of the ORION-13 Randomized Trial.

This study showed that inclisiran effectively and safely lowers LDL cholesterol in adolescents with homozygous FH, supporting early RNA interference-based lipid-lowering therapy in the youngest patients with severe genetic dyslipidemia.

## Abstract (original, from the publication)

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a genetic disease characterized by high levels of low-density lipoprotein cholesterol (LDL-C) present from birth, leading to early-onset and progressive atherosclerotic cardiovascular disease. Early treatment initiation is crucial for cardiovascular risk reduction; however, many patients do not reach LDL-C treatment goals. Inclisiran, a small interfering RNA targeting hepatic PCSK9 (proprotein convertase subtilisin/kexin type 9), is effective and well tolerated in adult patients with hyperlipidemia; however, it has not yet been studied in pediatric patients. METHODS: Herein we report results of the 1-year, double-blind, placebo-controlled part of the phase 3 study ORION-13 (Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Homozygous Familial Hypercholesterolemia) in adolescents with HoFH. This 2-part multicenter study included 13 patients ≥12 to <18 years of age with a genetic diagnosis of HoFH (excluding LDL [low-density lipoprotein] receptor [LDLR] null/null genotypes) and elevated LDL-C levels (>130 mg/dL) on maximally tolerated statin treatment, with or without other lipid-lowering therapies. Eligible patients were randomized 2:1 to receive either 300 mg of inclisiran sodium or placebo, administered on days 1, 90, and 270. The primary end point was the mean percentage change in LDL-C from baseline to day 330. RESULTS: The mean age of patients was 14.8 years, and mean baseline LDL-C was 272 mg/dL. The placebo-adjusted mean (95% CI) percentage change in LDL-C from baseline to day 330 was -33.3% (-59.2% to -7.3%). Six of 9 (66.7%) inclisiran-treated patients (versus 1 of 4 [25%] on placebo) achieved a >15% reduction in LDL-C, and 5 of 9 (55.6%) inclisiran-treated patients (versus none on placebo) achieved a >20% reduction. The placebo-adjusted mean (95% CI) percentage change in PCSK9 from baseline to day 330 was -60.2% (-79.8% to -40.7%); corresponding changes in apolipoprotein B, non-high-density lipoprotein cholesterol, and total cholesterol were -23.0%, -32.7%, and -27.8%, respectively. No serious adverse events, treatment discontinuations because of adverse events, or deaths occurred. No new safety findings were reported. CONCLUSIONS: In a 1-year randomized controlled study (part 1 of ORION-13), inclisiran was effective in lowering LDL-C in adolescents with HoFH and was well tolerated. These results support inclisiran as a potentially useful addition for the treatment of adolescents with HoFH and a minimum of LDLR residual activity. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04659863.

Auteurs: Albert Wiegman, Amy L Peterson, Robert A Hegele, Eric Bruckert, Anja Schweizer, Anastasia Lesogor, Yibo Wang, Joep Defesche

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Bron: Circulation, https://doi.org/10.1161/CIRCULATIONAHA.124.073233. Bijgewerkt 2026-07-03T13:30:41Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.