FDA Approves Oral Berotralstat for Pediatric HAE, With Jolanta Bernatoniene, PhD

The US Food & Drug Administration (FDA) has approved berotralstat (ORLADEYO) oral pellets for long-term prophylaxis of hereditary angioedema (HAE) in children aged 2 to 11 years. The approval, announced by BioCryst on December 12, 2025, marks the first and only oral, once-therapy indicated for long-term prevention of HAE attacks in this age group.1,2

“Up until now, we had huge unmet needs for this patient group,” Jolanta Bernatoniene, PhD, lead investigator of the APeX-P trial in the United Kingdom and from Bristol Royal Hospital for Children, told HCPLive. “Those patients were managed with injections, and as you can imagine, those injections caused significant negative impact on the patients, on the families, [and] was difficult to manage from clinical perspectives.”

Historically, long-term prophylaxis in children relied on subcutaneous monoclonal antibodies, such as lanadelumab or intravenous C1 esterase inhibitor concentrates, both of which can be challenging for pediatric patients and caregivers. Frequent injections are associated with needle anxiety, treatment reluctance, and substantial caregiver burden.

“[The berotralstat approval is a] significant achievement because these are little sprinkles, very easy to administer,” Bernatoniene continued.

Berotralstat’s oral formulation offers a meaningful shift in care. The medication is administered as small pellets that can be sprinkled onto non-acidic food, simplifying dosing and improving treatment acceptance. Berotralstat is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein that can prevent HAE attacks by reducing the activity of the plasma kallikrein.

The FDA decision was supported by efficacy and safety data from the APeX-P trial, which evaluated weight-based dosing across pediatric age groups. Interim and long-term results demonstrated rapid and sustained reductions in HAE attack rates, with mean monthly attack rates reduced to 0, and more than half of patients remaining attack-free for up to 1 year. The interim data showed that, at a steady state, berotralstat reached peak concentration at a median of 3.9 hours (range, 0.9 – 6.0 hours).

No clinically meaningful differences in efficacy were observed across age, sex, or disease severity subgroups. Additionally, no cardiovascular safety concerns, including QT prolongation, were observed in the pediatric population, according to Bernatoniene. Ongoing extension studies will continue to monitor long-term safety and effectiveness for up to 5 years.

Clinicians anticipate that berotralstat’s approval will prompt updates to national and international HAE treatment guidelines and influence first-line prophylactic strategies for children, particularly younger patients for whom injectable therapies pose significant challenges.

When asked how the berotrolstat approval may impact future drug development, Bernatoniene said that there is always room for improvement. Although berotralstat is effective and easy to administer, it remains a once-daily treatment.

“[It] would be easier for the patients if we can administer [the treatment] less frequently, so perhaps oral formulation, but once a month or once every 3 months,” she said. “This is still [a] daily medication to remember for the family when they have very busy lives. Every drug will have its niche, so the indications and prescribing [have] to be discussed… in partnership with children age-appropriate and their families.”

Bernatoniene has no relevant disclosures.

References

1. Derman C. FDA Approves Oral Berotralstat for Children Aged 2 – 11 Years with HAE. HCPLive. December 12, 2025. Accessed January 15, 2026. https://www.hcplive.com/view/fda-approves-oral-berotralstat-children-aged-2-11-years-hae

2. 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. Published December 12, 2025. Accessed December 12, 2025. https://ir.biocryst.com/news-releases/news-release-details/biocryst-announces-fda-approval-orladeyor-berotralstat-oral