This study evaluates the long-term safety and efficacy of evinacumab, an angiopoietin-like 3 inhibitor, in adolescent and adult patients with homozygous familial hypercholesterolemia (HoFH). The study was a single-arm, open-label Phase 3 trial that included 116 patients (46 evinacumab-naïve and 70 evinacumab-continue) who received intravenous evinacumab 15 mg/kg every 4 weeks for up to 2.5 years. The primary outcome was the incidence and severity of treatment-emergent adverse events (TEAEs) during the open-label treatment period (OLTP). Efficacy outcomes included changes in LDL cholesterol, apolipoprotein B, non-HDL cholesterol, total cholesterol, and fasting triglycerides. Key findings include: - Evinacumab significantly reduced LDL-C levels by an average of 43.6% at Week 24, with sustained reductions up to Week 48. - The safety profile was generally well-tolerated, with most TEAEs being mild or moderate in severity. - The most common TEAEs were nasopharyngitis, headache, and influenza-like illness. - No clinically significant changes in liver function parameters were observed. - The reduction in LDL-C was maintained across various patient subgroups, including age, sex, race, LDLR genotype, background lipid-lowering therapy (LLT), and baseline lipoprotein(a) levels. The study supports the long-term safety and efficacy of evinacumab in reducing LDL-C levels in patients with HoFH, regardless of treatment duration, age, sex, race, LDLR genotype, and background LLT.This study evaluates the long-term safety and efficacy of evinacumab, an angiopoietin-like 3 inhibitor, in adolescent and adult patients with homozygous familial hypercholesterolemia (HoFH). The study was a single-arm, open-label Phase 3 trial that included 116 patients (46 evinacumab-naïve and 70 evinacumab-continue) who received intravenous evinacumab 15 mg/kg every 4 weeks for up to 2.5 years. The primary outcome was the incidence and severity of treatment-emergent adverse events (TEAEs) during the open-label treatment period (OLTP). Efficacy outcomes included changes in LDL cholesterol, apolipoprotein B, non-HDL cholesterol, total cholesterol, and fasting triglycerides. Key findings include: - Evinacumab significantly reduced LDL-C levels by an average of 43.6% at Week 24, with sustained reductions up to Week 48. - The safety profile was generally well-tolerated, with most TEAEs being mild or moderate in severity. - The most common TEAEs were nasopharyngitis, headache, and influenza-like illness. - No clinically significant changes in liver function parameters were observed. - The reduction in LDL-C was maintained across various patient subgroups, including age, sex, race, LDLR genotype, background lipid-lowering therapy (LLT), and baseline lipoprotein(a) levels. The study supports the long-term safety and efficacy of evinacumab in reducing LDL-C levels in patients with HoFH, regardless of treatment duration, age, sex, race, LDLR genotype, and background LLT.