Berotralstat Cuts HAE Attack Burden in APeX-P Interim Analysis, With Jolanta Bernatoniene, MD, PhD

Children with hereditary angioedema (HAE) experienced sustained reductions in moderate and severe attacks over 48 weeks of oral berotralstat therapy, according to interim data from the phase 3 APeX-P study presented at the 2026 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in Philadelphia.1

In an interview at the meeting, Jolanta Bernatoniene, MD, PhD, from Bristol Royal Hospital for Children, discussed the clinical implications of the findings and how an oral long-term prophylaxis option may shift pediatric HAE management.

“It was [a] significant reduction,” Bernatoniene said. “For example, at the baseline, the median attack rate [was] almost 0.96. We've seen very early and sustained reduction to almost 0.”

APeX-P is an ongoing, open-label study evaluating the pharmacokinetics, safety, and efficacy of berotralstat, an oral plasma kallikrein inhibitor, in children with HAE. Participants remained on standard of care for 12 weeks before initiating berotralstat, allowing for within-patient comparisons.

The study enrolled 29 children aged 3 to 11 years. During the standard-of-care period, patients reported a median of 0.96 total monthly attacks, including 0.33 moderate and 0.31 severe attacks per month. After initiating berotralstat, reductions were observed as early as the first month of treatment. Over 48 weeks, the median monthly rate of moderate attacks decreased to 0.16, while severe attacks declined to 0.0.

Beyond attack frequency, the overall symptom burden also improved. During standard of care, patients experienced HAE symptoms on a median of 9% of days (range, 0%–40%). Over 48 weeks of berotralstat treatment, this fell to a median of 3% of days (range, 0%–10%).

Pediatric onset was common and early. Bernatoniene said that the median age of disease onset in the study population was approximately 2 years, and most children presented with symptoms before 6 years old. These findings underscore the need for effective long-term prophylaxis options in younger patients, who may experience substantial disease burden during critical developmental years.

The safety profile was favorable. Adverse events were consistent with prior berotralstat studies, and no grades 3 or 4 drug-related adverse events were reported. No patients discontinued therapy because of adverse events.

The approval of berotralstat by the US Food and Drug Administration (FDA) in December for this age group marks the first oral long-term prophylaxis option for children under 12 years of age with HAE.2 Previously available prophylactic therapies required subcutaneous or intravenous administration, which can impose a significant burden on patients and families. Berotralstat is administered as small oral pellets that can be sprinkled and are easy for caregivers to deliver.

“Patients are happy, parents are happy, clinicians are happy [with berotralstat],” Bernatoniene said. “In practice, the drug is very well accepted already by the families, by the clinicians. It’s already approved by [the] FDA. It’s [going to] … probably [be] first line recommended treatment for [HAE] for the children less than 12.”

References

1. Bernatoniene J, Bourgoin-Heck M, Cancian 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. Journal of Allergy and Clinical Immunology. 2026;157(2):AB39. doi:https://doi.org/10.1016/j.jaci.2025.12.120

2. Derman C. FDA Approves Oral Berotralstat for Children Aged 2 – 11 Years with HAE. HCPLive. January 5, 2026. Accessed on March 2, 2026. https://www.hcplive.com/view/fda-approves-oral-berotralstat-children-aged-2-11-years-hae.