Clinical Benefits Associated With Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia

Homozygous familial hypercholesterolemia (HoFH), characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) due to severely impaired LDL-C clearance from circulation, remains challenging to treat. Here, we investigated clinical benefits of monoclonal antibody, evinacumab, inhibiting angiopoietin-like 3, recently approved in children with homozygous familial hypercholesterolemia.

This retrospective, observational study included 13 children with homozygous familial hypercholesterolemia on oral lipid-lowering therapy and assessed their attainment of LDL-C goal, need for lipoprotein apheresis (LA), and cardiac plaque formation at initiation of evinacumab and at follow-up of 2.0 (1.3-3.0) years.

Evinacumab, initiated at age 11 (8.5-13.5) years, increased number of patients reaching LDL-C goal from none before initiation to 9 of 13 (69%; P=0.004) at follow-up. Mean±SD LDL-C at follow-up was 111 (44) mg/dL, compared with 206 (61) mg/dL before evinacumab (mean difference, -95 mg/dL [95% CI, -142 to -47]; P<0.001). Before initiation of evinacumab, 11 of 13 children received LA with average interval of 7.8 days. At follow-up, LA frequency decreased in 7 of 11 children with average interval of 18.9 days; increase between LA sessions was 11.0 days (3.5-18.5; P=0.008), 42% longer session interval. For 3 (15%) children, due to evinacumab initiation, LA remained dispensable over the course of treatment. Coronary computed tomography angiography showed plaque stabilization (n=5), regression (n=3), and no formation (n=2), in 10 of 13 (77%) children, and plaque progression in 3 (23%) children.

Add-on evinacumab increased number of children with homozygous familial hypercholesterolemia reaching and maintaining LDL-C goal, concomitant reduction in LA frequency, and in most patients, stabilization or improvement in coronary computed tomography angiography findings.