Berotralstat has been shown in a pivotal phase 3 randomized controlled trial to significantly reduce the frequency and duration of angioedema attacks when used as LTP in patients with type 1 and 2 HAE-C1-INH.25, 26, 27 However, no randomized controlled trials of berotralstat in patients with HAE-nC1-INH have been conducted. This evidence concerns the gene COL18A1 and angioedema.