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Oral berotralstat for hereditary angioedema prophylaxis in patients aged 2 to <12 years: APeX-P interim results
Jolanta Bernatoniene1, Mélisande Bourgoin-Heck2, Mauro Cancian3
1Paediatric Immunology and Infectious Disease Department, Bristol Royal Hospital for Children, Bristol, United Kingdom.
Insights
Oral berotralstat offers a well-tolerated, effective long-term prophylaxis for hereditary angioedema (HAE) in young children. This study shows significant reductions in HAE attack rates in patients under 12 years old.
Area of Science:
- Pharmacology and Therapeutics
- Genetics and Rare Diseases
- Pediatric Medicine
Background:
- Hereditary angioedema (HAE) is a rare genetic disorder often presenting in childhood, with current long-term prophylaxis (LTP) options for those under 12 requiring parenteral administration.
- Berotralstat, an oral small-molecule plasma kallikrein inhibitor, is approved for HAE prophylaxis in patients aged 12 and older.
Purpose of the Study:
- To assess the safety and efficacy of oral berotralstat as a long-term prophylaxis (LTP) for hereditary angioedema (HAE) in pediatric patients aged 2 to <12 years.
- The APeX-P trial (NCT05453968) represents the largest study of LTP in this specific pediatric HAE population.
Main Methods:
- Patients underwent a 12-week standard of care period prior to initiating berotralstat.
- Pharmacokinetics, safety, and efficacy of oral berotralstat were evaluated through a planned interim analysis.
- The study included 29 pediatric patients with HAE.
Main Results:
- The median age of participants was 8.0 years, with 82.8% experiencing symptom onset before age 6.
- Berotralstat demonstrated favorable pharmacokinetic parameters, with a median Tmax of 3.9 hours.
- No serious drug-related adverse events, deaths, or discontinuations due to adverse events were reported. HAE attack rates were significantly reduced from a median of 0.96 attacks per 4-week period during standard of care to 0 attacks per 4-week period by week 48.
Conclusions:
- Oral berotralstat is well-tolerated in pediatric patients with HAE aged 2 to <12 years.
- The treatment led to early and sustained reductions in hereditary angioedema attack rates.
- Berotralstat provides a promising oral prophylactic option for younger HAE patients.
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.
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