The goal of HAE prophylaxis is to minimize the burden of disease, including the number of attacks and improve quality of life. Berotralstat, an approved, oral once-daily prophylactic treatment for HAE, was shown to reduce attack frequency in the Phase 3, APeX-2 study (NCT03485911). Here we report the long-term efficacy and quality of life (QoL) data for patients treated with berotralstat 150mg in the APeX-2 study.

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 into an open-label part 3 on berotralstat 150mg. QoL was assessed using the validated AE-QoL; decrease in score indicates an improvement in QoL (score range 0-100, where 100 is worst possible impairment). For this analysis, patients were included if they completed 96 weeks in the study.

Seventy patients completed 96 weeks of treatment: 21 patients randomized to berotralstat 150mg in part 1, 12 patients transitioned from placebo to berotralstat 150mg in part 2, and 37 patients transitioned from berotralstat 110mg to 150mg in part 2 or 3. Patients received berotralstat 150mg for a median of 695 (range: 252-1192) days. Attacks rates remained consistently low, with a mean (SEM) attack rate after 4 weeks of treatment with berotralstat 150 mg of 1.1 (0.17) attacks/month which continued to improve through 24 weeks (0.8 [0.17]), 48 weeks (0.7 [0.15]), and 96 weeks (0.5 [0.22]) of treatment. Median attack rates were 1.0 attacks/month after 4 weeks and 0.0 attacks/month after 24, 48, and 96 weeks. Clinically meaningful improvements in QoL were seen in all domains of the AE-QoL questionnaire at all timepoints. The largest improvement was observed in the functioning category (23.5-point mean improvement from baseline, mean score at Week 96: 15.4).

These data show that oral berotralstat 150mg is an effective HAE prophylactic therapy that reduces HAE attack rates and improves quality of life in patients with HAE.