On December 12, 2025, the FDA approved BioCryst's berotralstat (ORLADEYO) prophylactic oral pellets for pediatric patients aged 2 to <12 years with hereditary angioedema (HAE), according to an announcement from the pharmaceutical company. The approval makes berotralstat the first targeted oral prophylactic therapy available to children under the age of 12 years with HAE.^1,2

The rare, inherited disease is characterized by unpredictable, potentially life-threatening recurrent swelling attacks most commonly affecting the extremities, face, abdomen, and larynx. Symptoms often begin in childhood and before puberty, with the earlier age of symptom onset significantly correlating to increased perceived severity and overall negative life impact.²

Today’s pediatric approval of [berotralstat) offers a welcome oral preventive choice for children living with HAE and provides families and clinicians with an important option for shared decision-making that matches treatment with patient needs,” said Anthony J. Castaldo, CEO and chairman of the US Hereditary Angioedema Association.¹

Phase 3 APeX-P trial data supported berotralstat approval

The NDA and subsequent approval were supported by positive, interim data from the phase 3 APeX-P (NCT05453968) study, evaluating pharmacokinetics (PK), safety, and tolerability of berotralstat in patients 2 to <12 years. The data were presented at the 2025 American Academy of Allergy, Asthma & Immunology (AAAAI) / World Allergy Organization Joint Congress in March, with results demonstrating a consistent safety profile across the age group as well as early and sustained reductions in monthly attack rates.²

The trial was 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 prior coverage from Contemporary Pediatrics,³ 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 the interim analysis.²

According to the poster presentation presented at AAAAI, there were 29 patients with a median age of 8 (3-11) years, of whom 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.

"Pediatric patients with HAE can experience significant burdens that are related to their condition and treatment, including HAE attacks requiring urgent medical care," said Jolanta Bernatoniene, FRCPCH, PhD, the primary investigator of the APeX-P trial, in a previous Q&A interview with 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 a significant impact on mental health and other developmental aspects of life experienced by young pediatric patients who live with HAE."³

Click here for more data on berotralstat and additional commentary from Bernatoniene.

References:

1. BioCryst announces FDA approval of ORLADEYO (berotralstat) oral pellets, first and only oral prophylactic treatment for patients with HAE aged 2 to <12 years. BioCryst Pharmaceuticals. Published December 12, 2025. Accessed December 12, 2025. https://www.globenewswire.com/news-release/2025/12/12/3204568/29446/en/BioCryst-Announces-FDA-Approval-of-ORLADEYO-berotralstat-Oral-Pellets-First-and-Only-Oral-Prophylactic-Treatment-for-Patients-with-HAE-Aged-2-to-12-Years
2. Fitch J. FDA accepts NDA for berotralstat in HAE patients aged 2 to 11 years. Contemporary Pediatrics. Published May 14, 2025. Accessed September 10, 2025. https://www.contemporarypediatrics.com/view/fda-accepts-nda-for-berotralstat-in-hea-patients-aged-2-to-11-years
3. Fitch J. AAAAI: Berotralstat reduces monthly hereditary angioedema attack rates in children. Contemporary Pediatrics. Published March 5, 2025. Accessed September 10, 2025. AAAAI: Berotralstat reduces monthly hereditary angioedema attack rates in children