Efficacy and safety of inclisiran in adolescents with heterozygous familial hypercholesterolaemia (ORION-16): a two-part, randomised, multicentre clinical trial

Wiegman, A; Peterson, AL; Bruckert, E; Defesche, JC; Schweizer, A; Bergeron, J; Chueca, MJ; Roeters van Lennep, JE; Santos, RD; Schwab, KO; Lesogor, A; Zhang, S; Hegele, RA

doi:10.1016/s2213-8587(25)00351-1

Lipids & metabolic liver disease

Efficacy and safety of inclisiran in adolescents with heterozygous familial hypercholesterolaemia (ORION-16): a two-part, randomised, multicentre clinical trial

Lancet Diabetes EndocrinolPublished 27 Jan 2026Randomised controlled trial

Primary result · LS mean percentage change in LDL-CResultBetween-group difference −28.5 % 95% CI −35.8 to −21.3

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Authors' conclusion

In adolescents with HeFH, inclisiran was effective in lowering LDL cholesterol, with sustained efficacy over 2 years, and was well tolerated. These results support inclisiran as a potentially useful addition for the treatment of adolescents with HeFH, providing an infrequent dosing regimen.

Study context

Population: Adolescents (aged 12 to <18 years) with heterozygous familial hypercholesterolaemia (HeFH) and elevated LDL-C on maximally tolerated statin ± other lipid-lowering therapy; median age 15.1 years, 53% female, 91% Whiterandomised 2:1
Participants: 141 adolescents

Comparison: Inclisiran vs placebo
Inclisirann = 93
Placebon = 48reference
Primary endpoint: Percentage change in LDL-C from baseline
Follow-up: Day 330

Methodological detailstwo-part (1-year double-blind, 1-year open-label), phase 3, multicentre, 51 sites across 26 countries

Two-part (1-year double-blind, 1-year open-label)
Phase 3
Multicentre
51 sites across 26 countries

Primary result

LS mean percentage change in LDL-C

Between-group difference

−28.5 %

95% CI −35.8 to −21.3

P < 0.0001

Change by group

Inclisiran

−27.1

least squares mean · %

Placebo

1.4

least squares mean · %

Inclisiranvs Placebo

between-group difference −28.5 % (95% CI −35.8 to −21.3); P < 0.0001

As reported in the abstract

Further findings

Mean percentage change in LDL-C from baseline (Part 2, open-label inclisiran) · day 720

Mean % change in LDL-C from baseline, SD 24.0: −33.7%

Safety

Injection site reactions · Part 1

Inclisiran16%

Placebo6%

Injection site reactions — Injection site reactions in Part 2: 13 of 139: 9%

Injection site reactions · Part 1

All mild; none led to study drug discontinuation

Serious adverse events and deaths

Treatment-related serious adverse events: 0
Deaths: 0
Well tolerated, safety profile comparable to studies in adults

Original publication

Efficacy and safety of inclisiran in adolescents with heterozygous familial hypercholesterolaemia (ORION-16): a two-part, randomised, multicentre clinical trial. Lancet Diabetes Endocrinol. Published 27 January 2026. doi:10.1016/s2213-8587(25)00351-1

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