Evinacumab with or without lipoprotein apheresis in homozygous familial hypercholesterolaemia

Homozygous familial hypercholesterolaemia (HoFH) is characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C). Most individuals with HoFH do not reach LDL-C targets with standard lipid-lowering therapies (LLTs). However, low density lipoprotein receptor (LDLR)-independent LLTs have demonstrated effectiveness in these individuals.

This post hoc subanalysis examined concomitant use of two LDLR-independent treatments, lipoprotein apheresis (LA) and evinacumab (an angiopoietin-like 3 inhibitor), in participants with HoFH from three clinical studies of evinacumab. We included participants with HoFH who received 15 mg/kg evinacumab in any Regeneron-sponsored clinical study. Participants were stratified by concurrent LA treatment at study baseline. The primary outcome was mean change in LDL-C from baseline to Week 24. Other outcomes included change in LA frequency and safety. Outcomes were examined descriptively.

A total of 138 participants were included, 59 (43%) undergoing LA at baseline and 79 (57%) not undergoing LA at baseline. From baseline to Week 24, mean (standard deviation) LDL-C was reduced in participants undergoing LA at baseline (-42.9% [23.8]) and those who were not (-50.8% [30.5]). Reductions in LDL-C in both subgroups were observed across all examined timepoints. Among those undergoing LA at baseline, LA frequency was reduced in 17 (29%) participants and increased in two (3%) participants. Evinacumab was well-tolerated in both subgroups.

This study demonstrated considerable benefit of evinacumab for individuals with HoFH, with or without concurrent LA. Evinacumab appeared to lessen LA burden for some individuals. This analysis suggests that LA and evinacumab can be combined without compromising efficacy or safety.