LONG-TERM EFFICACY OF EVINACUMAB IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: RESULTS FROM SUBGROUP ANALYSES

Pharmacologic Therapy Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of early-onset atherosclerotic cardiovascular disease. Despite treatment with multiple lipid-lowering therapies (LLTs), most patients with HoFH do not attain guideline-recommended LDL-C treatment goals. In a phase 3 trial (NCT03409744), evinacumab, an angiopoietin-like 3 inhibitor, substantially reduced mean LDL-C by 43.6% from baseline to Week 24. Here, we report on the long-term LDL-C lowering efficacy of evinacumab analyzed by patient subgroups from the open-label treatment period (OLTP) of this phase 3 trial. This single-arm, open-label, phase 3 study (NCT03409744) comprised patients with HoFH aged ≥12 years who were evinacumab-naïve or had previously received evinacumab in other trials. The study included a run-in period (≤10 weeks), a screening period (2 weeks), an OLTP (≤192 weeks), and a follow-up period (24 weeks). In the OLTP, all patients received intravenous evinacumab 15 mg/kg every 4 weeks alongside optimized LLT. Overall, 116 patients were enrolled with a mean (standard deviation [SD]) age of 38.8 (15.9) years. The proportion of male and female patients was similar (50.9% vs 49.1%, respectively). Most patients were White (69.0%) or Asian (10.3%). At baseline, mean (SD) LDL-C was 261.0 (160.1) mg/dL. Evinacumab reduced mean (SD) LDL-C from baseline to Week 96 by 57.6% (16.7%), 36.4% (54.6%), and 38.0% (52.9%) in patients <18 years of age, patients ≥18 years of age, and overall, respectively. Among female and male patients, mean (SD) LDL-C reduction from baseline to Week 96 was 48.8% (32.3%) and 30.5% (62.6%), respectively. Mean (SD) LDL-C reduction from baseline to Week 96 was 43.1% (36.9%) in patients with null-null variants in either the low-density lipoprotein receptor (LDLR) gene or the low-density lipoprotein receptor adapter protein 1 (LDLRAP1) gene; mean (SD) LDL-C reduction was 35.1% (62.4%) in patients with non-null variants in LDLR or LDLRAP1. From baseline to Week 96, reductions in LDL-C with evinacumab were observed irrespective of background LLT (Figure). In patients with HoFH, evinacumab showed substantial and sustained LDL-C reduction irrespective of age, sex, LDLR genotype, and background LLT.

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