Oral Berotralstat May Reduce Symptom Burden in Pediatric HAE

Berotralstat was well-tolerated and seemed to durably reduce hereditary angioedema (HAE) attacks, in findings from the APeX-P open-label study.

Data from the study were presented at the 2025 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress, February 28-March 3, in San Diego, California, by Jurga Bernatoniene, PhD, professor, Lithuanian University of Health Sciences.

HCPLive spoke with Bernatoniene while at the congress to learn more about APex-P, berotralstat, and how the therapy could potentially benefit the HAE population.

HCPLive: Can you give some background on berotralstat and the APeX-P trial?

Jurga Bernatoniene, PhD: Berotralstat is an oral, once-daily plasma kallikrein inhibitor for prophylaxis to prevent HAE attacks in adults and pediatric patients 12 years and older. HAE is a rare, inherited disease characterized by repeated painful and unpredictable attacks of severe submucosal and/or subcutaneous swelling in various parts of the body.

APeX-P is an open-label trial evaluating berotralstat in patients two to <12 years of age with HAE. The study was designed to collect pharmacokinetic data to inform appropriate weight ranges and doses for children to match the exposure of berotralstat seen in adult patients. Secondary objectives were to assess the safety and tolerability and describe the effectiveness of berotralstat in these patients.

Of note, APeX-P is the largest trial to evaluate a prophylactic therapy for HAE in patients two to <12 years of age, and enrollment was completed ahead of schedule and included more than the initial target number of participants.

What did you find in the APeX-P study?

Bernatoniene: The results from APeX-P show berotralstat was well tolerated in pediatric patients enrolled in the study, with early and sustained reductions in monthly attack rates, and no new safety signals identified beyond those previously described in prior adult and adolescent trials.

Specifically, the median (range) and mean (±SEM) monthly attack rates in the standard-of-care period were 0.96 (0–5.0) and 1.5 (±0.2) attacks/month, respectively. After one month of taking berotralstat, median and mean monthly attack rates dropped to 0 (0-4.0) and 0.5 (±0.2), and the median monthly attack rate remained at 0 through month 12 (month 12 range: 0-1.7); the mean monthly attack rate at month 12 was 0.3 (±0.1).

In APeX-P, we observed that children with HAE are experiencing severe swelling attacks at a very young age, with a median age of HAE symptom onset at two years. These findings support an earlier age of symptom onset and need for HAE prophylaxis than has generally been understood.

How do you think berotralstat could benefit the HAE population?

There are currently limited therapeutic options for pediatric patients with HAE under the age of 12, which are on-demand or long-term prophylaxis therapies administered either through subcutaneous injection or intravenous infusion. These routes of administration can be challenging, burdensome, and time consuming for patients and their caregivers.

Treatment through these routes of administration may cause caregivers and pediatric patients with HAE to feel nervous, overwhelmed, and stressed, which can become problematic because these emotions are known to trigger HAE attacks. This can also cause some physicians to hesitate to prescribe long-term prophylaxis to their young patients.

The oral granule formulation of berotralstat being evaluated in APeX-P could help reduce the treatment burden on children with HAE that is associated with currently available long-term prophylaxis therapies administered either intravenously or through subcutaneous injection or infusion. The oral granule formulation is designed to be less invasive for children to take and caregivers to administer. The granules, housed in a packet, are sprinkle-like in appearance and size and can be poured directly into the mouth and swallowed immediately with water or milk, or sprinkled over a spoonful of soft, non-acidic food, for more convenient treatment.

I am encouraged by the response to the results that were presented at the 2025 AAAAI/WAO Joint Congress, and I believe this new formulation of berotralstat has the potential to significantly reduce the treatment burden for children and families impacted by HAE. Also, I have personally experienced significant positive impact of berotralstat on the lives of children with HAE and their families, including significant improvement in their quality of life. The children were able to participate in their school and after school activities with no significant interruption.