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

Two Part (Double-blind Inclisiran Versus Placebo [Year 1] Followed by Open-label Inclisiran [Year 2]) Randomized Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Inclisiran in Adolescents (12 to Less Than 18 Years) With Homozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol (ORION-13)

This was a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in adolescents with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDL-C).

This was a two-part (double-blind, inclisiran versus placebo [Year 1] followed by open-label inclisiran [Year 2]) multicenter study in adolescents (aged 12 to < 18 years) with HoFH and elevated LDL-C (> 130 mg/dL; 3.4 mmol/L) on stable, individualized, optimal standard of care (SoC) background lipid-lowering therapy (including maximally tolerated statin treatment, at the Investigator's discretion) to evaluate the safety, tolerability, and efficacy of inclisiran in this pediatric patient population.

Following an approximately 4-week screening/run-in period, the study had 2 sequential parts as follows:

Part 1/Year 1: 12 months double-blind, parallel group period, in which participants were randomized in a 2:1 ratio to receive either inclisiran sodium 300 mg subcutaneous (s.c.) or placebo. The primary endpoint was assessed at Day 330.

Part 2/Year 2: 12 months single arm, open-label follow-up period, with all participants receiving inclisiran sodium 300 mg s.c.

Inclusion Criteria:

• Homozygous Familial Hypercholesterolemia (HoFH) diagnosed by genetic confirmation
• Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
• On maximally tolerated dose of statin (investigator's discretion) with or without other lipid-lowering therapy; stable for ≥ 30 days before screening
• Male or female participants >=12 to <18 years of age at screening

Exclusion Criteria:

• Documented evidence of a null (negative) mutation in both LDLR alleles
• Heterozygous familial hypercholesterolemia (HeFH)
• Active liver disease
• Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
• Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening)
• Treatment with mipomersen or lomitapide (within 5 months of screening)
• Recent and/or planned use of other investigational medicinal products or devices