Inclisiran confers LDL–C-lowering benefit in adolescents with HoFH

In adolescents with homozygous familial hypercholesterolemia (HoFH), treatment with inclisiran appears to be safe and efficacious for reducing low-density lipoprotein cholesterol (LDL-C) levels, according to the results of the first part of the phase III ORION-13* trial.

ORION-13 was a two-part multicentre study that included 13 patients with an age range of ≥12 to <18 years, with a genetic diagnosis of HoFH (excluding LDL receptor [LDLR] null/null genotypes), and with elevated LDL-C levels (>130 mg/dL) despite receiving maximally tolerated statin treatment with or without other lipid-lowering therapies.

The patients were randomly assigned to receive either 300 mg of inclisiran sodium (n=9) or placebo (n=4), administered on days 1, 90, and 270 (part 1), followed by open-label inclisiran treatment for another year (part 2). The mean percentage change in LDL-C from baseline to day 330 was the primary endpoint. Safety and tolerability were also assessed.

The mean age of patients was 14.8 years, with 69.2 percent being female and 84.6 percent being White. The mean LDL-C level at baseline was 272 mg/dL.

Compared with placebo, inclisiran was associated with a 33.3-percent reduction (−59.2 percent to −7.3 percent) in LDL-C levels from baseline to day 330. LDL-C decreased by >15 percent in six (66.7 percent) patients in the inclisiran group and in one (25 percent) in the placebo group. A >20-percent reduction was achieved in five (55.6 percent) and 0 patients in the respective groups.

As for other outcomes, PCSK9 decreased by 60.2 percent from baseline to day 330 with inclisiran vs placebo. The corresponding changes in apolipoprotein B, nonhigh-density lipoprotein cholesterol, and total cholesterol were −23.0 percent, −32.7 percent, and −27.8 percent, respectively.

None of the patients experienced serious adverse events or discontinued treatment due to adverse events. There were no reports of deaths and new safety findings.

* Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Homozygous Familial Hypercholesterolemia