A subcutaneous, highly concentrated, volume-reduced C1-INH concentrate (C1-INH[SC]; HAEGARDA®; CSL Behring, Marburg, Germany) was approved by the US FDA in 2017 for routine prevention of HAE attacks in adolescents and adults [13] based on a phase 3, placebo-controlled crossover study, the Clinical Studies for Optimal Management of Preventing Angioedema with low-volume subcutaneous C1-inhibitor Replacement Therapy (COMPACT) trial (NCT01912456). This evidence concerns the gene SERPING1 and angioedema.