Oral berotralstat shows meaningful reductions in pediatric HAE attacks

In this interview with Contemporary Pediatrics, Jolanta Bernatoniene, MD, PhD, lead investigator at Bristol Royal Hospital for Children, discussed the clinical implications of interim 48-week data on oral berotralstat for children aged 2 to younger than 12 years with hereditary angioedema (HAE).

Bernatoniene emphasized that the reduction in moderate and severe monthly attack rates is clinically meaningful, particularly because prior studies had not focused extensively on attack severity. At baseline, the median rate of moderate to severe attacks was nearly 1 per month, which decreased to nearly 0 during treatment. This substantial decline signals not only fewer attacks overall but also, importantly, fewer debilitating episodes, an outcome that pediatricians should view as highly relevant in everyday practice when assessing disease control.

Beyond attack frequency, the decrease in symptomatic days—from a median of 9% under standard of care to 3% with berotralstat—has important functional implications. Bernatoniene noted that fewer symptomatic days translated into improved participation in school and extracurricular activities, as well as better overall quality of life. She observed firsthand that treatment allowed children to live more normally and reduced the psychosocial burden on families, describing the therapy as transformative for many trial participants.

Regarding treatment positioning, berotralstat represents the first and only oral long-term prophylaxis option for children younger than 12 years with HAE. Until now, pediatric options have been limited to injectable therapies administered subcutaneously every 2 to 4 weeks. Given children’s common aversion to needles, the availability of a noninjectable alternative may be particularly appealing. Bernatoniene underscored the importance of shared decision-making among clinicians, parents, and patients when considering transitioning from existing injectable prophylaxis.

Safety data from the interim analysis were reassuring. No grade 3 or 4 adverse events related to the drug were reported, and no patients discontinued therapy because of adverse effects. The medication, administered as pellets and taken with food, was described as well tolerated and easy to use.

From a practical perspective, Bernatoniene suggested that an oral plasma kallikrein inhibitor could improve adherence, reduce caregiver anxiety, lessen treatment burden, and help normalize daily life for children and their families managing HAE.

No relevant disclosures.

Reference

Bernatoniene J, Bourgoin-Heck M, Cacian M, et al. Oral berotralstat reduces the rate of moderate and severe attacks and percentage of days with HAE symptoms over 48 weeks in children aged 2 to less than 12 years: interim data from APeX-P. J Allergy Clin Immunol. 2026;157(2):AB39. doi:10.1016/j.jaci.2025.12.120