Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia

BACKGROUND: Evolocumab, a fully human monoclonal antibody that targets proprotein convertase subtilisin-kexin type 9 (PCSK9), is extensively utilized in adult patients to reduce low-density lipoprotein (LDL) cholesterol levels. However, its effects in pediatric patients with heterozygous familial hypercholesterolemia have been previously unknown.

METHODS: We conducted a 24-week, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of evolocumab in pediatric patients diagnosed with heterozygous familial hypercholesterolemia who had LDL cholesterol levels of 130 mg per deciliter (3.4 mmol per liter) or higher, despite receiving the maximally tolerated dose of lipid-lowering therapy. Patients aged 10 to 17 years were assigned to receive subcutaneous evolocumab (420 mg monthly) or placebo. Patients aged 6 to 9 years received subcutaneous evolocumab (420 mg monthly) or placebo in a 2:1 ratio. The primary end point of the trial was the percentage change from baseline in the LDL cholesterol level at week 24.

RESULTS: A total of 157 patients were enrolled, comprising 99 patients aged 10 to 17 years and 58 patients aged 6 to 9 years. At week 24, the mean (±SE) percentage change from baseline in the LDL cholesterol level was –38.3±2.2% in the evolocumab group, compared to +6.2±2.3% in the placebo group. This resulted in a statistically significant difference of –44.5 percentage points (95% confidence interval [CI], –50.7 to –38.4; P<0.001). Adverse events, including nasopharyngitis, headache, and influenza, occurred with similar frequency in both groups (73.1% in the evolocumab group and 72.4% in the placebo group). Injection-site reactions were observed in 5.8% of patients in the evolocumab group, while none occurred in the placebo group. No new safety concerns were identified during the 24-week study period.

CONCLUSIONS: In pediatric patients with heterozygous familial hypercholesterolemia, evolocumab demonstrated a significant reduction in LDL cholesterol levels and did not raise any new safety concerns over the 24 weeks of the study.

BACKGROUND: Evolocumab, a fully human monoclonal antibody that targets proprotein convertase subtilisin-kexin type 9 (PCSK9), is extensively utilized in adult patients to reduce low-density lipoprotein (LDL) cholesterol levels. However, its effects in pediatric patients with heterozygous familial hypercholesterolemia have been previously unknown.

METHODS: We conducted a 24-week, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of evolocumab in pediatric patients diagnosed with heterozygous familial hypercholesterolemia who had LDL cholesterol levels of 130 mg per deciliter (3.4 mmol per liter) or higher, despite receiving the maximally tolerated dose of lipid-lowering therapy. Patients aged 10 to 17 years were assigned to receive subcutaneous evolocumab (420 mg monthly) or placebo. Patients aged 6 to 9 years received subcutaneous evolocumab (420 mg monthly) or placebo in a 2:1 ratio. The primary end point of the trial was the percentage change from baseline in the LDL cholesterol level at week 24.

RESULTS: A total of 157 patients were enrolled, comprising 99 patients aged 10 to 17 years and 58 patients aged 6 to 9 years. At week 24, the mean (±SE) percentage change from baseline in the LDL cholesterol level was –38.3±2.2% in the evolocumab group, compared to +6.2±2.3% in the placebo group. This resulted in a statistically significant difference of –44.5 percentage points (95% confidence interval [CI], –50.7 to –38.4; P<0.001). Adverse events, including nasopharyngitis, headache, and influenza, occurred with similar frequency in both groups (73.1% in the evolocumab group and 72.4% in the placebo group). Injection-site reactions were observed in 5.8% of patients in the evolocumab group, while none occurred in the placebo group. No new safety concerns were identified during the 24-week study period.

CONCLUSIONS: In pediatric patients with heterozygous familial hypercholesterolemia, evolocumab demonstrated a significant reduction in LDL cholesterol levels and did not raise any new safety concerns over the 24 weeks of the study.