FDA Accepts BioCryst’s NDA for Berotralstat Oral Granules in Children With HAE

BioCryst announced on May 14, 2025, that the US Food and Drug Administration (FDA) accepted the New Drug Application (NDA) for berotralstat (ORLADEYO) oral granules in patients with hereditary angioedema (HAE) aged 2 to 11 years.1

The company also shared that the FDA granted berotralstat a priority application review, with a PDUFA target action date of September 12, 2025. If berotralstat gets approved, it would be the first targeted oral prophylactic therapy for patients with HAE aged < 12 years.

“…we believe this oral granule formulation of ORLADEYO could help children with HAE and their families better manage their condition and avoid the traumatic experience of acute attacks with emergency care or hospital stays,” Helen Thackray, chief research and development officer of BioCryst, said in a statement.

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. Just 1 capsule a day can prevent attacks by reducing the activity of plasma kallikrein. The FDA approved berotralstat in adults and children aged ≥ 12 years back in December 2020, and this treatment is commercially available in > 30 countries.

The NDA was based on positive interim data from APeX-P, the largest clinical trial to evaluate a prophylactic therapy for HAE in patients aged 2 to 11 years. These findings were presented at the 2025 American Academy of Allergy, Asthma, & Immunology/ World Allergy Organization Joint Congress in late February, early March.

The APeX-P trial showed berotralstat provided early and sustained reductions in monthly attack rates. Investigators observed an increase in QT prolongation at dosages over the recommended 150 mg once-daily dosage.

“As detailed in the results from APeX-P, we observed that participants experienced serious HAE attacks at a very early age, with a median age of HAE symptom onset of two years, which suggests there is a larger burden of disease at an earlier age than has been appreciated thus far,” Thackray added.1

Berotralstat was tolerable and had a consistent safety profile in children. Common adverse events included abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease. People with moderate or severe hepatic impairment received a reduced oral dosage of 110 mg daily with food.

Despite the NDA, the safety and effectiveness of berotralstat have not yet been established in children < 12 years.

BioCryst has filed its line extension application for the use of berotralstat oral granules in patients with HAE aged 2 to 11 years with the European Medicines Agency. The company plans to file in other global territories, such as Japan and Canada.

“We are excited to take another step closer to bringing ORLADEYO to younger pediatric patients with HAE,” said BioCryst President and Chief Executive Officer Jon Stonehouse in a statement.1 “We consistently hear from patients, caregivers, and physicians about their desire for a more convenient therapeutic option to treat young children with HAE, and we now may have the opportunity to bring this to them later this year.”

References

1. BioCryst Announces FDA Acceptance of NDA for ORLADEYO® (berotralstat) Oral Granules in Patients with Hereditary Angioedema Aged 2 to 11 Years. Biocryst. March 14, 2025. https://ir.biocryst.com/news-releases/news-release-details/biocryst-announces-fda-acceptance-nda-orladeyor-berotralstat. Accessed May 14, 2025.