Senior Director of Operation ECOGENE-21 Chicoutimi, Quebec, Canada
Background:
Background: Homozygous familial hypercholesterolemia (HoFH) is a rare condition associated with very premature atherosclerotic cardiovascular disease most often caused by bi-allelic pathogenic variants in the LDL-receptor (LDLR) gene. Evinacumab, an angiopoietin-like protein 3 (ANGPTL3) inhibitor that enhances lipoprotein clearance independently of LDLR function, has been approved for HoFH treatment based on the ELIPSE-HoFH clinical trial. Despite important sex-related disparities in lipid metabolism, females are still underrepresented in trials. With 116 enrolled patients, of which 49.1% were females, ELIPSE-OLE is the largest cohort of HoFH females involved in a clinical trial to date.
Objective: The aim of this study was to compare response to evinacumab in females and males in the ELIPSE OLE study.
METHODS AND RESULTS:
Methods: The ELIPSE OLE study aimed to assess safety and efficacy of evinacumab in HoFH patients aged ≥12 years, and included 57 females and 59 males on stable background lipid lowering treatments (LLT). Subjects received evinacumab 15 mg/kg intravenously every 4 weeks for up to 192 weeks. Primary efficacy endpoint was relative (%) and absolute change in LDL-cholesterol (LDL-C) from baseline to week 24. This post-hoc analysis compared baseline characteristics, LDL-C response to evinacumab, and safety of evinacumab between females and males. All p-values are nominal without any adjustments for multiple comparisons or other factors. Stata/MP (College Station, TX, USA) was used to perform the statistical analyses.
Results: There were no significant sex-specific differences in HoFH diagnostic criteria or pathogenic variants, demographics or background LLT, except for lomitapide which was used less frequently in females. Baseline LDL-C and non-HDL-C [mean (SD)] tended to be higher in females aged 18 to < 50 yrs than in males: 8.4 (5.4) vs 6.4 (3.5) mmol/L (p=0.07) and 9.0 (5.5) vs 6.9 (3.5) mmol/L (p=0.06), respectively. Evinacumab treatment substantially and incrementally decreased LDL-C and similar levels were reached by both males and females. Since baseline LDL-C tended to be higher among females, this translated in a trend to observe higher relative (%) decreased tended in females, irrespective of the baseline BMI, LDL-C levels, use of high-intensity statin or concomitant use of LDLR-independent treatments. Overall, evinacumab was well-tolerated, with no significant sex-specific differences in the prevalence of treatment emergent adverse effects. Higher prevalences of gastrooesophageal reflux disease and urinary tract infection were observed among females.
Conclusion:
Conclusions: Evinacumab substantially and incrementally decreased LDL-C and brough plasma concentrations to similar levels among males and females, regardless of genotype or background LLT
