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 aged 12 years and older.

Objective: To assess the long-term safety and efficacy of berotralstat in patients with HAE caused by 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 United States 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 by means of treatment-emergent adverse events 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.

Results: In APeX-S, 387 patients were enrolled and received berotralstat 150 mg (n = 287) or 110 mg (n = 100) from day 1. A total of 70 patients on berotralstat 110 mg crossed over to berotralstat 150 mg after a median (range) of 48 (46-71) weeks. Treatment-emergent adverse events 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 Angioedema Quality of Life Questionnaire 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 in preventing HAE attacks and improving QoL.

Clinical Trial Registration: This trial was registered at ClinicalTrials.gov as NCT03472040 (https://clinicaltrials.gov/study/NCT03472040).