Orladeyo safely prevents swelling attacks in young children with HAE
Biocryst to ask FDA to expand Orladeyo's approval to patients as young as 2
An oral granule formulation of Orladeyo (berotralstat) was safe and well tolerated, and able to reduce the rates of swelling attacks in children with hereditary angioedema (HAE), according to an interim analysis of an ongoing Phase 3 trial.
The open-label Phase 3 APeX-P trial (NCT05453968) is assessing the safety and pharmacological properties of once-daily Orladeyo oral granules in children with HAE, ages 2 to 11.
Findings were presented in a poster, titled “HAE Attack Rates in Pediatric Patients 2 to <12 Years of Age with Prophylactic Berotralstat: Results from Interim Analysis of APeX-P,” at the recent 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress.
Biocryst Pharmaceuticals, which markets Orladeyo, plans to submit an application to the U.S. Food and Drug Administration this year to expand the treatment’s approval to children as young as 2.
Orladeyo led to early and sustained reductions in monthly attack rates
“The data show the oral granule formulation of Orladeyo to be safe and well tolerated in the trial, with early and sustained reductions in monthly attack rates,” Helen Thackray, MD, chief research and development officer at Biocryst, said in a company press release.
HAE is characterized by swelling attacks caused by an overproduction of bradykinin, a signaling molecule that promotes blood vessel widening and increases permeability, causing fluid to leak out to nearby tissues and swelling to occur.
Orladeyo is an oral therapy that works by suppressing the activity of kallikrein, an enzyme that mediates the production of bradykinin. It is approved to prevent swelling attacks in people with HAE, 12 and older.
The therapy’s approval was mainly based on data from the Phase 3 APeX-2 trial (NCT03485911), which demonstrated the treatment significantly and sustainably reduced swelling attack rates.
The APeX-P trial has enrolled 29 children, who were a median age of 8 years, and 52% of them were boys. They were a median age of 2 years when their symptoms began, with most (82.8%) starting to show signs of HAE before the age of 6. The children were divided into four groups according to body weight at the time of enrollment.
After three months on standard of care treatment, the children started receiving Orladeyo for up to 144 weeks (nearly three years). The presented data were gathered at the time 17 participants had completed about one year of treatment.
Orladeyo was generally safe and well tolerated, with no new safety signals identified. Adverse events were consistent across different age groups and body weights.
The most commonly reported treatment-related adverse events were the common cold (27.6%), upper respiratory tract infection (24.1%), and headache (13.8%). There were no serious or drug-related severe adverse events, deaths, or treatment discontinuations due to adverse events.
Orladeyo reduced monthly attack rates to 0.3 after 1 year
Orladeyo also led to rapid and sustained reductions in monthly attack rates. During the initial 12-week period when the children were on standard of care treatment, they had a mean of 1.5 attacks per month. After one month of treatment with Orladeyo, the mean attack rate decreased to 0.5 attacks per month, and after one year, it reduced to 0.3 attacks per month.
“This interim analysis shows there is significant potential for an oral, once-daily prophylactic therapy to meaningfully impact the lives of pediatric patients with HAE … especially considering the burden of disease and injectable treatment currently experienced by these patients,” said Jolanta Bernatoniene, PhD, a pediatrician at the Bristol Royal Hospital for Children, in the U.K.
Biocryst also presented real-world data showing Orladeyo significantly reduced the rate of HAE attacks, in patients with HAE types 1 and 2 and in those with a rarer subtype, known as HAE type 3 or HAE with normal C1-INH.
“We continue to be encouraged by these real-world outcomes that show Orladeyo is having a meaningful impact on patients regardless of disease activity,” said Donald S. Fong, MD, chief medical officer of Biocryst.
Additional posters focused on the patient-reported impact of Orladeyo also demonstrated most participants had less frequent and less severe HAE attacks after starting treatment.
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