The goal of HAE prophylaxis is to minimize the burden of disease, including number of attacks, and reduce the burden of treatment. Berotralstat is an oral, once-daily, selective plasma kallikrein inhibitor that was shown to reduce attack frequency in the Phase 3 study, APeX-2 (NCT03485911). Here we report long-term data on injectable on-demand medication use in patients treated with berotralstat for 96 weeks in the APeX-2 trial.

A total of 121 subjects with HAE Type 1 or 2 were randomized 1:1:1 to berotralstat 110mg:150mg:placebo for 24 weeks (part 1). In part 2 (N=108), patients assigned to berotralstat in part 1 continued on the same blinded dose for an additional 24 weeks and patients assigned to placebo were re-randomized 1:1 to receive berotralstat 150mg or 110mg. Patients could continue onto the open-label part 3 during which all patients were transitioned to berotralstat 150mg. This analysis includes patients who received berotralstat 150mg through parts 1, 2, and 3 for a total of 96 weeks of treatment(n=21).

The number of attacks/month requiring treatment with injectable on-demand medication continuously declined over 96 weeks of treatment with berotralstat. At baseline, the mean (SEM) number of treated attacks was 2.2(0.42) attacks/month, which declined to 0.9(0.34) attacks/month at Week 24, 0.6(0.25) attacks/month at Week 48, and 0.4(0.15) attacks/month at Week 96, resulting in an 87% reduction at Week 96. In addition, the overall use of injectable on-demand medication continuously declined over time. At baseline a mean (SEM) of 2.8(0.54) doses/month of on-demand medication was used to treat attacks. This declined to 1.1(0.38) doses/month at Week 24, 0.8(0.31) doses/month at Week 48, and 0.4(0.18) doses/month at Week 96, resulting in an 88% reduction at Week 96.

Patients receiving oral berotralstat had fewer attacks that required treatment with injectable on-demand medication and used less on-demand medication (doses/month) to treat attacks. These data suggest that the use of oral berotralstat leads to an increase in needle-free days for patients with HAE due to the reduction in injectable on-demand medication use.