3105Evolocumab treatment in paediatric patients with homozygous familial hypercholesterolaemia: the Trial Assessing long-term Use of PCSK9 inhibition in Subjects with Genetic LDL disorders (TAUSSIG)

Abstract

Background: Homozygous familial hypercholesterolaemia (HoFH) is a genetic disorder characterised by minimal or no low-density lipoprotein receptor (LDLR) function, resulting in severely elevated LDL-cholesterol levels, and premature cardiovascular disease with onset often in childhood. The phase 3 open-label TAUSSIG study demonstrated that after 12 weeks of treatment with evolocumab, LDLcholesterol decreased from baseline by 21% among 106 patients with HoFH aged 13 to 68 years; these reductions were maintained through Week 48 and beyond. Purpose: We report results from 14 paediatric patients ≤18 years with HoFH enrolled in TAUSSIG. Methods: Patients age 13 to 17 years on stable LDL-cholesterol lowering therapy for ≥4 weeks received evolocumab 420 mg monthly; or if on apheresis, 420 mg biweekly to align with apheresis schedule. Dosing frequency could be increased to biweekly in non-apheresis patients after 12 weeks, at investigator discretion. Results: HoFH was genetically confirmed in all patients. All 14 had mutations in both LDLR alleles: 7 (50%) had ≥1 defective, 5 (36%) had unclassified, and 2 (14%) had negative overall LDLR status. All were taking statins with 12 (86%) on high-intensity statins, 13 (93%) also on ezetimibe, and 4 (29%) were on apheresis. Despite the young age, cardiovascular disease was common, with 29% having coronary artery disease. Baseline mean (SD) PCSK9 was 614 (175) ng/mL. Evolocumab reduced LDL-cholesterol by 11% (0.6 mmol/L, n=14) atWeek 12 and by 21% (1.4 mmol/L, n=10) in those not receiving apheresis, which was maintained through Week 48 (-23% [-1.9 mmol/L], n=10). Seven non-apheresis patients increased dosing to every 2 weeks, with an additional 10% (0.7 mmol/L) LDL-cholesterol reduction. Those with residual LDLR activity had a better response than patients with unclassified or negative LDLR (Table). Evolocumab was well tolerated, and no serious adverse events were reported. Conclusions: Evolocumab 420 mg monthly or biweekly safely achieved stable long-term reduction in LDL-cholesterol and provides an effective option to further lower LDL-cholesterol levels in paediatric patients with HoFH. (Figure Presented).