Berotralstat Reduces Use Of On-Demand Medication In Hereditary Angioedema (Hae) Patients Previously Treated With Prophylactic Therapies

The goal of HAE prophylaxis is to minimize the number of HAE attacks and the associated disease burden, including treatment with on-demand medications. Berotralstat is an oral once-daily selective plasma kallikrein inhibitor that has been shown to reduce attack frequency in a Phase 3 study (NCT03485911). This analysis evaluates reduction in on-demand medication in patients with prior prophylaxis. A double-blind, placebo-controlled study (APeX-2) randomized patients to berotralstat 110 mg (n=41):150 mg (n=40):placebo (n=40) daily for 24 weeks in Part 1. For this post hoc analysis, patients were grouped according to their prior prophylaxis: prior C1 esterase inhibitor (C1-INH), prior androgen, or no prior prophylactic medication. Prior C1-INH and prior androgen categories are not mutually exclusive. In patients with prior C1-INH prophylaxis (berotralstat 150 mg n=21; placebo n=16), the rate of use of on-demand treatment was significantly reduced vs placebo (-59.2%, p=0.002). Similar reductions were noted for patients with prior androgen use (berotralstat 150 mg n=22; placebo n=25) (-51.8%; p=0.004) and in patients without prior prophylaxis (berotralstat 150 mg n=10; placebo n=10) (-71.2%; p=0.019). The rate reduction corresponds to approximately 2.2 fewer doses of on-demand medication per month compared to placebo in patients with prior C1-INH use, 1.6 for those with prior androgen use, and 1.4 for those with no prior prophylaxis. Prophylactic treatment with oral berotralstat 150 mg resulted in significant reductions in on-demand medication compared to placebo irrespective of prior prophylactic treatment.