Oral berotralstat for hereditary angioedema prophylaxis in patients aged 2 to <12 years: APeX-P interim results.

BACKGROUND

Hereditary angioedema (HAE) is a rare genetic disorder with symptoms often appearing during childhood. Current approved long-term prophylaxis (LTP) for children aged <12 years requires parenteral administration. Berotralstat is an oral, small-molecule plasma kallikrein inhibitor, approved as prophylaxis of HAE attacks in patients aged 12 years or older.

OBJECTIVE

To evaluate oral berotralstat for the LTP of HAE in pediatric patients through APeX-P (NCT05453968), the largest trial of LTP in patients with HAE aged 2 to <12 years.

METHODS

Before berotralstat initiation, patients received standard of care for 12 weeks. Pharmacokinetics, safety, and efficacy of berotralstat were assessed in a planned interim analysis.

RESULTS

Median (range) age of patients (N = 29) was 8.0 (3-11) years, with 48.3% female. Median age at symptom onset was 2.0 years, and 82.8% of patients reported symptom onset before 6 years. Steady-state berotralstat median (range) Tmax was 3.9 (0.9-6.0) hours, geometric mean (coefficient of variation) Cmax was 204 ng/mL (40%), and AUC0-last was 915 ng•h/mL (42%). Most common treatment-emergent adverse events (AEs) were nasopharyngitis, upper respiratory tract infection, and headache. There were no drug-related grade 3/4 or serious AEs, deaths, or discontinuations related to AEs. Median (range) HAE attack rate during standard of care was 0.96 (0-5.0) attacks per 4-week period. Median (range) HAE attack rates for each 4-week period from day 1 to week 48 were 0 (week 4: 0-4.0; week 48: 0-1.7).

CONCLUSION

Oral berotralstat was well tolerated and resulted in early and sustained reductions in HAE attack rates.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05453968 and ClinicalTrialsRegister.eu Identifier: EU CTN 2024-511257-22-00.