Berotralstat Becomes First Oral Prophylactic for Pediatric Patients With Hereditary Angioedema

The FDA has approved the new drug application for an oral pellet formulation of berotralstat (Orladeyo; BioCryst), a once-daily prophylactic plasma kallikrein inhibitor, for pediatric patients aged 2 through less than 12 years with hereditary angioedema (HAE), according to a news release from BioCryst.¹

APeX-P Interim Results Demonstrate Efficacy of Pediatric Berotralstat

Interim results from the pivotal, ongoing phase 3 APeX-P clinical trial (NCT05453968) bolstered berotralstat’s clinical efficacy and safety profile on its path toward approval. In the trial, berotralstat demonstrated early and sustained reductions in monthly HAE attack rates. Median and mean monthly attack rates were reduced from 0.96 and 1.5 attacks per month in the standard-of-care period to 0 and 0.5 attacks per month following 1 month of taking berotralstat.^2-4

Crucially, the median monthly attack rate remained at 0 through month 12 of treatment; at month 12, the mean monthly attack rate was 0.3. Berotralstat demonstrated tolerability and safety in APeX-P, and no new safety signals were identified. There were also similar rates of AEs across all weights and ages, an important indicator of berotralstat’s ability to reduce HAE attacks in a series of age groups. The most reported treatment-emergent adverse event was nasopharyngitis.^2,3

“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,” Anthony J. Castaldo, CEO and chairman of the board of directors of the US Hereditary Angioedema Association, said in the news release.¹

Trial Methods and HAE Background

The study authors detailed methods of the APeX-P trial. Prior to initiating berotralstat, patients enrolled in the trial received standard-of-care treatment for 12 weeks, which could have included prophylaxis. The subsequent open-label period of berotralstat treatment is set to last for a total of 144 weeks. Results from this interim analysis were taken from 17 participants who had completed at least 48 weeks of treatment with berotralstat.^2,3

HAE often presents during childhood, with approximately 40% of children experiencing their first attack by the age of 5 years. The rare genetic condition presents as localized swelling of tissues underneath the skin and can be accompanied by signs of an allergic reaction. This swelling occurs due to leaking fluid from tiny blood vessels in the body, which can build up in nearby tissues and prevent blood from moving efficiently. In severe cases, HAE can cause severe complications like anaphylactic shock or bronchospasm.^5,6

Berotralstat was previously approved in a capsule formulation for patients 12 years and older to prevent HAE attacks and has since been approved in dozens of countries around the world. Now, a pediatric formulation of oral pellets can help younger patients struggling with the debilitating daily impacts of HAE attacks. The new formulation is sprinkle-like in nature, allowing it to be poured directly into a patient’s mouth and be quickly swallowed with fluids or sprinkled over a spoonful of soft food.¹

“As we mark 5 years since [berotralstat] 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,” Jon Stonehouse, CEO of BioCryst, said in the news release. “We couldn’t be more excited to bring this treatment option to these kids and their caregivers.”¹

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. News release. BioCryst. December 12, 2025. Accessed December 16, 2025. https://ir.biocryst.com/news-releases/news-release-details/biocryst-announces-fda-approval-orladeyor-berotralstat-oral

2. BioCryst announces positive results from APeX-P trial for Orladeyo (berotralstat) in pediatric patients with hereditary angioedema aged 2 to <12 years. News release. BioCryst. February 24, 2025. Accessed December 16, 2025. https://ir.biocryst.com/news-releases/news-release-details/biocryst-announces-positive-results-apex-p-trial-orladeyor

3. Bernatoniene J, Bourgoin-Heck M, Cancian M, et al. Oral berotralstat for hereditary angioedema prophylaxis in patients aged 2 to <12 years: APeX-P interim results. Ann Allergy Asthma Immunol. 2025;135(6):681-688.e3. doi:10.1016/j.anai.2025.07.012

4. Berotralstat treatment in children with hereditary angioedema (APeX-P). ClinicalTrials.gov. Updated September 10, 2025. Accessed December 16, 2025. https://clinicaltrials.gov/study/NCT05453968

5. Arakelians S, Tran N. Angioedema is an uncommon but serious condition. Pharmacy Times. January 4, 2021. Accessed December 16, 2025. https://www.pharmacytimes.com/view/angioedema-is-an-uncommon-but-serious-condition

6. Hereditary angioedema. Cleveland Clinic. Last updated March 28, 2025. Accessed December 16, 2025. https://my.clevelandclinic.org/health/diseases/hereditary-angioedema