(P235) COMPASSIONATE USE OF EVINACUMAB FOR THE TREATMENT OF HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA (HOFH) IN CHILDREN UNDER 5 YEARS OF AGE: CLINICAL EXPERIENCE

Background: HoFH is a rare genetic disorder characterized by extremely elevated LDL-C levels from birth, leading to premature atherosclerotic cardiovascular disease. Most lipid-lowering medications are not approved for use in pediatric patients, and none are approved for the treatment of children under 5 years of age. This represents an important unmet medical need.

METHODS AND RESULTS: This case series included 3 children < 5 years old treated with the angiopoietin-like 3 inhibitor evinacumab 15 mg/kg IV Q4W through a compassionate use (CU) program. Informed consent from the child’s caregiver was obtained prior to treatment initiation. LDL-C levels were compared before and during treatment and adverse events (AEs) were monitored. All patients initiated evinacumab before 5 years of age (Patient A: male, 1 year and 1 month; Patient B: male, 4 years and 4 months; Patient C: female, 4 years and 5 months). All 3 patients showed a large reduction in LDL-C levels after initiating evinacumab, with reductions sustained up to the last reported dose: Patient A: 70.6% reduction in LDL-C at Week 36; Patient B: 31.4% reduction in LDL-C at Week 46 and plasmapheresis frequency was able to be reduced during the treatment period (Figure 1); Patient C: 63.7% reduction in LDL-C at Week 46. Two patients who presented with xanthomas prior to treatment had almost complete resolution. Evinacumab was well-tolerated; no serious AEs were reported, and no new safety concerns were identified, consistent with its established safety profile in older pediatric, adolescent, and adult patients.

Conclusion: Real-world data indicate a promising effect of evinacumab 15 mg/kg in the 3 CU patients < 5 years old, with tolerance, safety, and efficacy findings consistent with approved indications for older patients with HoFH. Evinacumab affords the potential to delay initiation or reduce the frequency of pheresis treatments while delaying the onset of atherosclerosis in these very young patients.