Abstract 12066: The Long-Term Safety and Efficacy of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

Abstract

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder characterized by marked elevations in LDL-C and premature atherosclerotic cardiovascular disease (ASCVD). EU guidelines recommend LDL-C treatment goals of <55 mg/dL and <70 mg/dL for pts with HoFH with and without ASCVD, respectively. Evinacumab (EVIN; an angiopoietin-like 3 inhibitor) significantly reduced LDL-C and was generally well tolerated in pts with HoFH during the 24-week double-blind treatment period (DBTP) of a pivotal Phase 3 study (NCT03399786). Methods: This post-hoc analysis assessed the long-term effect of EVIN on LDL-C goal attainment in pts with HoFH who participated in the subsequent 24-week open-label treatment period (OLTP) of the pivotal Phase 3 study. All pts received intravenous EVIN 15 mg/kg every 4 weeks. Efficacy by background lipid lowering medication (LLM) subgroups and the effect of EVIN on eligibility for apheresis were also assessed. Results: In total, 65 pts entered the OLTP and 64 pts (98.5%) received OL EVIN. Overall, 50.0% achieved LDL-C <100mg/dL, 31.7% achieved LDL-C <70 mg/dL and 23.3% achieved LDL-C <55 mg/dL at Week 48 (end of OLTP) (Figure 1). For the subgroup with ASCVD (n=36), 50.0%, 37.5% and 31.3% achieved LDL-C <100 mg/dL, <70 mg/dL and <55 mg/dL, respectively. Overall, 43.1%, 24.6% and 38.5% of pts qualified for apheresis at baseline and did not qualify for apheresis at Week 48 (using new US, US and EU criteria); no patient discontinued apheresis. EVIN markedly reduced LDL-C, irrespective of background LLM. Overall, treatment-emergent adverse events (TEAEs) occurred in 47 pts (73.4%) during the OLTP. Serious AEs (all unrelated to EVIN) were reported by 7 pts (10.9%), none led to death or EVIN discontinuation. Conclusions: EVIN enabled 31.7% of all pts to achieve LDL-C <70 mg/dL and 31.3% of those with ASCVD to achieve LDL-C <55 mg/dL. EVIN markedly reduced the proportion of pts qualifying for apheresis.