Long-term safety and efficacy of once-daily berotralstat in patients with hereditary angioedema: APeX-S final results.

Background: Berotralstat is a once-daily oral medication for the prophylaxis of hereditary angioedema (HAE) attacks in patients ≥12 years.

Objective: APeX-S aimed to assess the long-term safety and efficacy of berotralstat in patients with HAE due to C1 inhibitor deficiency.

Methods: APeX-S was a global, open-label Phase 2 study (NCT03472040) assessing berotralstat 150 and 110 mg for up to 96 weeks in the US and 240 weeks elsewhere. The primary objective was long-term safety and tolerability; secondary objectives included efficacy and impact on quality of life (QoL) of berotralstat. Safety was evaluated via treatment-emergent adverse events (TEAEs) and laboratory analyses. Efficacy was assessed using the number and rate of HAE attacks, durability of response, and number and proportion of days with angioedema symptoms. QoL was evaluated using the Angioedema Quality of Life Questionnaire (AE-QoL).

Results: In APeX-S, 387 patients were enrolled and received berotralstat 150 mg (n=287) or 110 mg (n=100) from Day 1. Seventy patients on berotralstat 110 mg crossed over to berotralstat 150 mg after a median (range) of 48 (46-71) weeks. TEAEs up to 240 weeks were reported by 334 patients (86.3%); the most common being nasopharyngitis (23.8%), headache (14.7%), diarrhea (14.5%), upper respiratory tract infection (12.9%), and abdominal pain (11.1%). Treatment with berotralstat led to improvements in HAE attack rates and AE-QoL scores up to Week 96, with greater improvements observed in patients who received berotralstat 150 mg from Day 1.

Conclusion: This study supports the long-term safety of berotralstat and its efficacy at preventing HAE attacks and improving QoL.