However, no liver abnormalities in adults and adolescent patients with HoFH have been observed with evinacumab over a longer trial duration (>2 years).47 This is particularly relevant given the recent discontinuation of the vupanorsen program.48 Vupanorsen, an antisense oligonucleotide that inhibits ANGPTL3 protein synthesis, was in part discontinued due to dose-dependent increases in hepatic fat and marked elevations in alanine aminotransferase and aspartate aminotransferase that were observed in a phase 2b trial of adult patients with dyslipidemia.48 This evidence concerns the gene GPT and metabolic syndrome.