1-year trial data: Orladeyo cuts swelling attacks in young children
New data also show burden HAE places on kids, caregivers
Written by |
Daily treatment with Orladeyo (berotralstat) oral granules led to early and sustained reductions in swelling attack rates in young children with hereditary angioedema (HAE), according to one-year interim data from an ongoing Phase 3 trial.
The data, together with additional analyses on disease burden and patient experience, were presented by Biocryst Pharmaceuticals, the company marketing the therapy, at the American College of Allergy, Asthma & Immunology’s annual scientific meeting, held last month in Orlando, Florida.
Orladeyo was initially approved in the U.S. and other regions for routine prevention, or prophylaxis, of swelling attacks in HAE patients aged 12 and older. The U.S. Food and Drug Administration recently extended its approval to children ages 2-11, authorizing a new pellet formulation.
“Treatment with ORLADEYO oral granules showed a sustained reduction in HAE attack rates over one year, and the high continuation rate suggests meaningful disease benefit and strong tolerability in this cohort,” Jolanta Bernatoniene, PhD, pediatrician at Bristol Royal Hospital for Children in the U.K., said in a company press release.
HAE is a genetic disorder marked by recurrent episodes of severe swelling affecting the skin, gastrointestinal tract, and airway. These attacks are triggered by the excessive production of bradykinin, a signaling molecule that increases blood vessel permeability, causing fluid to leak out to nearby tissues and resulting in swelling.
New data confirm benefits
Orladeyo works by suppressing kallikrein, an enzyme involved in bradykinin production, thereby helping prevent swelling attacks.
The open-label APeX-P trial (NCT05453968) is evaluating the safety and pharmacological properties of the therapy in up to 29 children aged 2 to 11 with HAE. Participants are receiving once-daily Orladeyo oral granules at doses adjusted according to body weight for up to 144 weeks, or nearly three years. The trial findings served as the basis for the recent FDA approval for children younger than 12, with the study expected to run through early 2027.
Earlier data showed the therapy to be well tolerated and effective, reducing attack rates within the first month of treatment and lowering the percentage of days with HAE symptoms as early as three months, with improvements maintained through one year in children who reached that point in the study.
The new interim trial data shared by the company confirm Orladeyo’s benefits for that population.
According to Biocryst, 65.5% of children were attack-free after one month of treatment, and 70.4% were attack-free after one year, with the median monthly attack rate falling to zero early on and remaining at that level for 11 of the first 12 months of the study.
Children remained on Orladeyo as long as 63.9 weeks, or about 15 months, and 93.1% of participants completed at least 48 weeks, or roughly 11 months, of treatment.
Data also revealed that HAE attacks often begin at a young age. Children were diagnosed at a median age of 2, and most (about 83%) had symptoms before they turned 6.
The therapy was safe and well tolerated over one year of treatment, with no new safety concerns identified. The most commonly reported side effect was nasopharyngitis, an inflammation of the nose and throat typically associated with cold-like symptoms.
In a series of three posters, the company also detailed new analyses showing the substantial psychosocial burden HAE places on young children and their caregivers.
The data indicated that symptoms typically begin in early childhood, with healthcare providers reporting that about 80% of children develop symptoms by age 8. Caregivers also noted attacks about every three months, which significantly disrupt children’s daily life — including school attendance, participation in sports, and social activities — and negatively affect mental health.
Healthcare providers reported high levels of concern that young patients could develop anxiety (84%), depression (76%), social isolation (76%), or academic underachievement (64%) as a result of living with HAE.
Caregivers also described significant impacts on their own health, including anxiety, stress, disrupted sleep, and reduced self-care.
Emergency department and hospital visits were common, with more than three-quarters of adolescents and nearly half of caregivers reporting at least one emergency department visit before the age of 12. Patients and caregivers often described these visits as stressful due to delays in care and challenges with injectable medications — experiences that, for some adolescents, contributed to lasting fear of hospitals or needles.
“Our psychosocial data elucidate that HAE attacks typically begin well before puberty and can have a profoundly negative impact on the mental health and quality of life of both children and their caregivers,” said Donald S. Fong, MD, chief medical officer of Biocryst.
