Berotralstat Consistently Demonstrates Reductions in Attack Frequency in Hereditary Angioedema (HAE) Irrespective of Baseline Attack Rate: Subgroup Analysis from the APeX-2 Trial

Abstract

Berotralstat is an oral plasma kallikrein inhibitor in development for HAE attack prophylaxis. HAE is characterized by unpredictable, episodic attacks; some patients experience frequent attacks without treatment. This analysis sought to understand whether baseline attack frequency correlates with responder rates with berotralstat. 121 patients were randomized to berotralstat 110 mg:150 mg:placebo daily for 24 weeks in a phase 3 double-blind, placebo-controlled study (NCT03485911). This post hoc analysis examined the reduction of HAE attacks by baseline attack rate Cohort 1: < 2 attacks/month; Cohort 2: ≥2 to < 4 attacks/month; Cohort 3: ≥4 attacks/month. In Cohort 1, median baseline attack rates per month were 1.3 (berotralstat 150 mg; n= 10) and 1.7 (placebo; n= 12) which declined to 0.41 and 1.3, respectively. In Cohort 2, median baseline attack rates per month were 2.7 (berotralstat 150 mg; n=20) and 3.1 (placebo; n=21) which declined to 1.2 and 2.7, respectively. For Cohort 3, median baseline attack rates per month were 5.2 with berotralstat 150 mg (n=10) and 4.5 with placebo (n=6) and declined to 1.9 and 2.5, respectively. In Cohorts 1, 2, and 3, treatment with berotralstat 150 mg resulted in a ≥50% relative reduction in attack rate in 70%, 55%, and 50% of patients, respectively. In addition, 60%, 45%, and 50% of patients, respectively, had ≥70% relative reduction in attack rate. These results demonstrate consistent responder rates with berotralstat, adding a potential oral prophylactic option to the treatment armamentarium for physicians.