FDA Approves Oral Berotralstat for Children Aged 2 – 11 Years with HAE

BioCryst announced on Friday, December 12, 2025, that the US Food & Drug Administration (FDA) approved berotralstat (ORLADEYO) oral granules for patients with hereditary angioedema (HAE) aged 2 – 11 years.1 This follows berotralstat’s 2020 FDA approval for the prevention of HAE attacks in adults and children aged ≥ 12 years.2

“Pediatric patients living with HAE can experience significant burdens, not only from the disease itself but also from its treatments, affecting their physical, psychosocial, and developmental well-being,” said Raffi Tachdjian, MD, associate clinical professor of medicine & pediatrics at the David Geffen School of Medicine, University of California Los Angeles. “This new oral pellet formulation of ORLADEYO provides a more easily administered long-term-prophylactic option to help children with HAE better manage their disease, especially when the experience of infusions or injections is not ideal.”

This past year the FDA approved many treatments for HAE—garadacimab-gxii (Andembry) in June, sebetralstat (Ekterly) in July, and donidalorsen (Dawnzera) in August—but all for adults.3 Numerous experts said that, despite these approvals, a critical HAE care gap was the limited treatment options for children under 12 years.

“We are excited to make ORLADEYO oral pellets available to children living with HAE. The use of prophylactic therapy has been limited among younger children compared to adults, in part because of the lack of appropriate, less burdensome treatment options. ORLADEYO oral pellets have the potential to change how a new generation of children with HAE and their caregivers manage this condition, giving them more freedom to live a normal life,” said Charlie Gayer, president and chief commercial officer of BioCryst.

Until now, children under 12 with HAE could only take Berinert (plasma-derived esterase inhibitor (human)), Cinryze (C1 esterase inhibitor (human)), haegarda (c1 esterase inhibitor subcutaneous (human)), and lanadelumab-flyo (Takhzyro).4 Of these previously approved treatments, only Berinert and lanadelumab-flyo are approved to target HAE attacks in children as young as 2 years old.5,6 This berotralstat approval adds another treatment option for children experiencing HAE attacks.

Berotralstat, a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein, is the first oral therapy designed specifically to prevent attacks of HAE.7 Taking 1 capsule a day can prevent attacks by reducing the activity of plasma kallikrein.

The pediatric approval was based on positive interim data from APeX-P, the largest clinical trial evaluating prophylactic therapy for HAE in 29 patients aged 2 to 11 years (48.3% females; mean age, 8 years, mean HAE onset age, 2 years).7,8 The study, led by Jolanta Bernatoniene, MD, PhD, from Bristol Royal Hospital for Children in the UK, showed berotralstat provided early and sustained reductions in monthly attack rates. At a steady state, berotralstat reached peak concentration at a median of 3.9 hours (range, 0.9 – 6.0 hours).8 Investigators noted an increase in QT prolongation at dosages over the recommended 150 mg daily dose.7

Berotralstat was well tolerated and had a consistent safety profile in children as compared to adults. Common adverse events included abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease.7

“As we mark 5 years since ORLADEYO first transformed care for those with HAE ages 12 and older, this approval extends the benefits of oral prophylactic therapy to a vulnerable and important part of the HAE community, children ages 2 to less than 12. We couldn’t be more excited to bring this treatment option to these kids and their caregivers,” said Jon Stonehouse, chief executive officer of BioCryst. “ORLADEYO has been prescribed to more than 3,500 patients in the U.S. to date, and we’re honored to now bring an oral pellet formulation to children and their caregivers, answering the community’s heartfelt call for a long-term prophylactic treatment option that meets the unique needs of children."

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

2. Kunzmann K. FDA Approves Berotralstat as First Oral Hereditary Angioedema Prophylaxis. Hcplive. Published December 4, 2020. Accessed December 9, 2025. https://www.hcplive.com/view/fda-approves-berotralstat-oral-hereditary-angioedema-prophylaxis

3. Soteres D, Tachdjian R, Manning M. Rare Disease, Rapid Progress: FDA's HAE Approvals in 2025 Signal Changing Course. HCPLive. Published December 3, 2025. Accessed 9, 2025. https://www.hcplive.com/view/rare-disease-rapid-progress-fda-hae-approvals-in-2025-signal-changing-course. Accessed 9, 2025.

4. US Hereditary Angioedema Association. Haea.org. Published 2020. https://www.haea.org/pages/p/treatments

5. FDA Expands Lanadelumab for Preventing HAE Attacks in Younger Children. HCPLive. Published February 4, 2023. Accessed 9, 2025. https://www.hcplive.com/view/fda-expands-lanadelumab-preventing-hae-attacks-younger-children.

6. U.S. FDA Approves CSL Behring’s Berinert® as the First and Only Pediatric Treatment for Hereditary Angioedema (HAE). Global Newsroom | CSL. Published July 18, 2016. Accessed December 9, 2025. https://newsroom.csl.com/2016-07-18-U-S-FDA-Approves-CSL-Behrings-Berinert-R-as-the-First-and-Only-Pediatric-Treatment-for-Hereditary-Angioedema-HAE

7. Derman C. FDA Accepts BioCryst’s NDA for Berotralstat Oral Granules in Children With HAE. HCPLive. Published May 14, 2025. Accessed December 9, 2025. https://www.hcplive.com/view/fda-accepts-biocryst-s-nda-for-berotralstat-oral-granules-in-children-with-hae

8. Derman C. Oral Berotralstat Shows Strong Safety, Efficacy in Young Children with HAE. HCPLive. Published August 5, 2025. Accessed December 9, 2025. https://www.hcplive.com/view/oral-berotralstat-shows-strong-safety-efficacy-in-young-children-with-hae