Jolanta Bernatoniene, PhD

FDA Approves First Oral Preventive Treatment for Pediatric HAE, With Jolanta Bernatoniene, PhD

 has approved berotralstat (ORLADEYO) oral pellets for long-term prophylaxis of 

 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.

“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 

“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.

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

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

Videos

Berotralstat becomes the first once-daily oral prophylactic option for long-term prevention of hereditary angioedema in children aged 2–11 years.

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

Credit: Bristol Royal Hospital for Children

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 Jolanta Bernatoniene, PhD, pediatric infectious disease department of Bristol Royal Hospital for Children.

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

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

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.

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.

Articles

Jolanta Bernatoniene, PhD, discussed positive results from the APeX-P study of oral berotralstat in children with hereditary angioedema.