Jolanta Bernatoniene, FRCPCH, PhD

Results reported from the ongoing phase 3 APeX-P study—evaluating pharmacokinetics (PK), safety, and effectiveness of berotralstat (ORLADEYO; BioCryst) in patients aged 2 to <12 years with hereditary angioedema (HAE)—revealed berotralstat treatment resulted in early and sustained reductions of monthly HAE attack rates.¹

Data was presented at the 2025 American Academy of Allergy Asthma & Immunology (AAAAI) and World Allergy Organization (WAO) Joint Congress meeting, held in San Diego, California, from February 28 through March 3, 2025.

Background on APeX-P and berotralstat

APeX-P (NCT05453968) is berotralstat among a cohort of patients aged 2 to < 12 years with HAE with C1-inhibitor deficiency (HAE-C1INH) and reporting ≥2 HAE attacks within 6 months prior to enrollment, according to the poster presented at AAAAI.^1,2

The study's primary investigator Jolanta Bernatoniene, FRCPCH, PhD, and colleagues noted the rare inherited disease is characterized by unpredictable, potentially life-threatening recurrent swelling attacks most commonly affecting the extremities, face, abdomen, and larynx.¹

Symptoms often begin in childhood, before puberty, and earlier age of HAE symptom onset significantly correlates with increased perceived severity and overall negative life impact.

"Pediatric patients with HAE can experience significant burdens that are related to their condition and treatment, including HAE attacks requiring urgent medical care," said Bernatoniene in a statement to Contemporary Pediatrics.

"HAE can have a negative impact on daily activities, including missed school days, diminished academic performance, and missed engagement in sports and social opportunities," said Bernatoniene. "In addition to physical burden, there can be significant impact on mental health and other developmental aspects of life experienced by young pediatric patients who live with HAE."

Berotralstat is an oral, small-molecule plasma kallikrein inhibitor currently approved for prophylaxis of HAE attacks in adults and adolescents aged 12 years and older.¹

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, which are administered either intravenously or through subcutaneous injection or infusion," said Bernatoniene.

"The oral granule formulation is designed to be less invasive for younger patients to take and caregivers to administer," she added. "The granules 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 that fits their daily routines."

APeX-P results

Prior to berotralstat initiation, patients continued standard of care for 12 weeks. Study dosing for Cohort 1 was 150 mg capsules. For Cohorts 2, 3, and 4, oral granules were given as doses of 108 mg, 96 mg, and 78 mg, respectively. PK characterization, HAE attack rates up to Month 12 (Week 48), and incidence of adverse events (AEs) were assessed in this interim analysis, stated the study authors.

According to the poster presentation, there were 29 patients with a median age of 8.0 (3-11) years, of which 48% were female. The median age of symptom onset was 2.0 (0.3-8.0) years, with 83% occurring before age 6.

During the standard of care period the median monthly attack rate was 0.96 (0-5.0). From months 1 to 12, the median HAE monthly attack rate was 0/ Ranges at month 1 and month 12 were 0–4.0 and 0–1.7, respectively, according to results.

The APeX-P trial is the largest to date evaluating a prophylactic therapy for HAE. With these interim analysis results, BioCryst is on track to submit a new drug application with the FDA for the oral granule formulation of berotralstat in 2025. If approved, it will become oral, once-daily prophylactic therapy for HAE for children under the age of 12.

Below, Jolanta Bernatoniene provided the key takeaway from the available study results presented at AAAAI.

Bernatoniene:

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

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

I personally have had a positive experience as a clinician to see such a significant benefit in terms of the clinical improvement of children with HAE and positive impact on the quality of life of children and their families.

Therefore, this oral, once-daily prophylactic therapy could help children with HAE and their caregivers better manage their disease and participate in daily activities that are important to them."

References:

1. Bernatoniene J, Bourgoin-Heck M, Yang WH, et al. HAE Attack Rates in Pediatric Patients 2 to <12 Years of Age with Prophylactic Berotralstat: Results from Interim Analysis of APeX-P. Poster. Presented at: 2025 American Academy of Allergy Asthma & Immunology and World Allergy Organization Joint Congres. February 28 - March 3, 2025. San Diego, California.

2. Berotralstat Treatment in Children With Hereditary Angioedema (APeX-P). ClinicalTrials.gov. October 15, 2024. Accessed March 5, 2025. https://clinicaltrials.gov/study/NCT05453968