(CSEMP034) CASE SERIES OF CANADIAN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA TREATED WITH ANGPTL3 INHIBITOR, EVINACUMAB

Abstract:

Background: Homozygous familial hypercholesterolemia (HoFH) is an ultrarare, life-threatening condition characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-C) due to biallelic LDL receptor variants. Patients have an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Traditional lipid-lowering agents are minimally effective and the gold standard treatment is serial apheresis. Recently, an angiopoietin-like protein 3 (ANGPTL3) inhibitor, evinacumab, was introduced as a promising new treatment for HoFH. It was FDA-approved in 2021, but is currently available in Canada only through clinical trials or special access programs.
Case Presentations: The first five Canadian HoFH patients to receive evinacumab via special access are presented. Their mean age is 25.0 years (SD = 12.3). As of December 2022, they have received evinacumab 15 mg/kg intravenously every four weeks for a mean of 19.2 months (SD = 10.5). Their mean incremental LDL-C reduction is 43.5% (SD = 8.14) on evinacumab along with reduced apheresis frequency for most on serial apheresis. Safety labs for all patients are normal. Brief case summaries are as follows: (a) Patient A is a 37-year-old man with severe ASCVD on a statin, ezetimibe, evolocumab and LDL-apheresis. Since starting evinacumab 38 months ago, his time-averaged LDL-C decreased by 42.9%, from 4.76 to 2.72 mmol/L. (b) Patient B is a 17-year-old male with elevated LDL-C levels despite being on a statin, ezetimibe and LDL-apheresis. After 21 months on evinacumab, his time-averaged LDL-C reduced by 37.8%, from 8.75 to 5.44 mmol/L. (c) Patient C is a 30-year-old woman with ASCVD on a statin and ezetimibe, but not apheresis. She has been on evinacumab for 18 months with a 54.1% reduction in LDL-C, from 11.43 to 5.25 mmol/L. (d) Patient D is a 36-year-old man with ASCVD on a statin, ezetimibe, evolocumab, lomitapide and plasmapheresis. He started evinacumab 9 months ago with a 50.7% decrease in time-averaged LDL-C, from 4.34 to 2.14 mmol/L. (e) Patient E is a 5-year-old boy with HoFH and xanthomas on a statin, ezetimibe and plasmapheresis. After 10 months of treatment with evinacumab, his time-averaged LDL-C decreased by 31.9%, from 9.45 to 6.44 mmol/L.

Discussion: Five HoFH patients with distinctive histories, baseline treatments and ASCVD have all shown marked improvement in LDL-C levels with a mean reduction of 43.5% on evinacumab on top of existing therapy. Overall, observations from our case series suggest that evinacumab is an effective new treatment for HoFH, a life-threatening condition with few therapeutic options.