Abstract 14270: The Effect of Evinacumab on Apheresis Eligibility in Patients With Homozygous Familial Hypercholesterolemia

Abstract

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Evinacumab, a fully human monoclonal antibody against angiopoietin-like protein 3, has demonstrated approximately 50% reductions in LDL-C in HoFH patients when added to maximally tolerated lipid-lowering therapies. Objective: In this post-hoc analysis, we assessed the effect of evinacumab on the eligibility for apheresis using predefined US and EU apheresis criteria. Methods: This was a double-blind, placebo-controlled, 24-week phase 3 trial (NCT03399786) that randomized patients 2:1 to evinacumab 15 mg/kg intravenously every 4 weeks (Q4W; n=43) or placebo (n=22). We assessed the proportion of patients who met per protocol US apheresis criteria (LDL-C ≥300 mg/dL), newer US criteria for FH (LDL-C ≥300 mg/dL or LDL-C ≥160 mg/dL with coronary heart disease or peripheral artery disease) and per protocol EU apheresis criteria (LDL-C >160 mg/dL [primary prevention] or >120 mg/dL [secondary prevention]) at baseline and week 24. Results: Under the newer US criteria (2018), 62.8% (n=27) of evinacumab-treated patients and 54.5% (n=12) placebo-treated patients qualified for apheresis at baseline (Table). Following 24 weeks of treatment, 48.8% of all evinacumab versus 9.1% of all placebo patients no longer qualified for apheresis. Similar results were observed using EU apheresis criteria, where 46.5% of evinacumab-treated patients shifted from qualifying for apheresis at baseline to not qualifying at week 24, compared with 4.5% of placebo-treated patients. The majority of evinacumab (65.1%) and placebo (68.2%) patients did not qualify for per protocol US apheresis at baseline, however a shift of 27.9% and 9.1% was observed, respectively. Conclusions: Evinacumab has the potential to reduce the need for apheresis in patients with HoFH.

Angiopoietin-like proteins inhibitors: New horizons in the treatment of atherogenic dyslipidemia and familial hypercholesterolemia

“…Raal [ 47 ] during the American College of Cardiology Congress in 2020 presented the results of a study involving 65 patients, 12 years of age or older with HoFH and plasma LDL concentrations greater than 70 mg/dL at screening. After an 8-week lead-in period to stabilize basic lipid-lowering therapy, 43 patients were randomized to receive evinacumab 15 mg/kg iv every 4 weeks and 22 to placebo group.…”

“…Evinacumab has been shown to significantly reduce plasma LDL (by 47.1%), apoB 100 by 36.9%, non-HDL cholesterol by 51.7%, total cholesterol by 48.4%, and triglycerides by 50.4% (p < 0.0001 for all) concentrations. However, the study drug had no effect on Lp(a) plasma concentration ( Table 1 ) [ 47 ].…”

Hyperlipidemia in Children and Adolescents

“…Newer medications have also been released such as evinacumab, evolocumab, and ezetimibe for use in patients that fail to reach goal LDL levels with statins or are otherwise noncompliant with daily oral medications. [52][53][54][55]…”

“…There were no deaths in either group. 52 This monoclonal antibody was also well studied for use in refractory hypercholesterolemia in young adults. 53…”

Сучасна Гіполіпідемічна Терапія (Огляд Літератури)

“…При застосуванні евінакумабу у пацієнтів з гомозиготною сімейною гіперхолестеринемією (дослідження ELIPSE) на тлі застосування статинів внутрішньовенна інфузія евінакумабу (15 мг/кг маси тіла) кожні 4 тижні знижувала рівень ХС ЛПНЩ у плазмі крові на 49% та рівень ТГ у плазмі крові на 50%. [19]. У дослідженні за участю пацієнтів з рефрактерною гіперхолестеринемією, незважаючи на прийом інгібіторів PCSK9 та при максимальній переносимій дозі статинів, з або без езетимібу (середнє значення ХС ЛПНЩ 150 мг/дл), евінакумаб знижував рівень ХС ЛПНЩ у плазмі крові більш ніж на 50% у максимальній дозі (450 мг/тиждень вводиться підшкірно в дозі 15 мг/кг маси тіла, що вводиться внутрішньовенно з інтервалом 4 тижні) [20].…”