APeX-P Trial of Orladeyo Now Enrolling Children 2–11 With HAE

Phase 3 study testing approved therapy's safety, efficacy in youngsters

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Enrollment has begun in APeX-P, a Phase 3 trial designed to evaluate the effects of Orladeyo (berotralstat) in up to 20 children, ages 2–11, with hereditary angioedema (HAE).

The open-label study, sponsored by BioCryst Pharmaceuticals, will provide data on Orladeyo’s safety, pharmacological properties, and ability to prevent HAE attacks in young children.

The trial is now recruiting youngsters with HAE at sites in Canada, Austria, France, and Spain. Locations in Germany, Israel, Italy, Poland, Romania, and the U.K., as well as an additional site in France, are expected to open soon.

Following APeX-P’s completion, BioCryst plans to ask regulatory authorities to expand the use of Orladeyo as a treatment to prevent HAE attacks in pediatric patients.

“Today’s announcement marks a very important step in our continuing efforts to reduce the burden of therapy for people living with HAE around the world with oral, once-daily Orladeyo,” Ryan Arnold, BioCryst’s chief medical officer, said in a press release.

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Trial testing Orladeyo in young children

In this type of trial, both participants and researchers know the exact treatment patients are receiving. Open-label studies typically are conducted to gather additional information about the effects of a therapy on the intended patient population.

“Pediatric patients are a particularly important group where the challenges posed by disease and treatment can be significant to these children and their families, especially given the uncertainty they face as they are newly diagnosed during childhood,” Arnold said.

“It is imperative that we strive to help normalize patients’ lives, as early experiences can have a lasting impact on how HAE is perceived — and managed — for their entire lifetimes,” Arnold added.

Orladeyo is approved in the U.S. and several other countries for HAE patients ages 12 and older.

Taken once a day as an oral capsule, the therapy prevents swelling attacks by suppressing the activity of kallikrein, an enzyme that is overactive in HAE patients. Lowering kallikrein’s activity reduces the production of a pro-inflammatory molecule called bradykinin that drives swelling attacks.

Because the medication is taken orally, the therapy may be preferred by young children over standard infusion treatments, such as those given by subcutaneous (under-the-skin) or intravenous (into-the-vein) injections.

Early data from the Phase 3 APeX-2 trial (NCT03485911) and the open-label Phase 2/3 APeX-S trial (NCT03472040) supported Orladeyo’s approvals in older patients.

According to data, about a year of Orladeyo sustainably reduced monthly HAE attacks and lessened the need for other standard-of-care therapies. Treated patients had more days without symptoms, better treatment satisfaction, and improved quality of life than those receiving a placebo.

Recent reports also showed that HAE patients who switched to Orladeyo from other preventive treatments experienced fewer swelling attacks overall.

The most commonly reported side effects were back pain and digestive tract reactions. These occurred mostly in the early stages of treatment and became less frequent over time, resolving on their own.

We are excited by the opportunity to introduce this new pediatric formulation of Orladeyo that could significantly reduce the treatment burden for children and families impacted by HAE.

The new APeX-P trial (NCT05453968) begins with a 12-week standard-of-care treatment period, followed by a 48-week (almost one year) period of once-daily Orladeyo, with continuation up to 144 weeks (nearly three years).

Enrolled patients will be divided into four dose groups based on body weight. Two higher-weight groups will be enrolled first and assessed in parallel. Before enrolling lower-weight groups, a data monitoring committee will review data from higher-weight patients to confirm the therapy’s safety.

The study’s primary goal is to assess Orladeyo’s pharmacokinetic properties, measuring how fast the medication is absorbed, how long it remains active, and how fast it is cleared from the body. Secondary outcomes include evaluating the occurrence and severity of adverse events (side effects) and HAE attacks.

“We are excited by the opportunity to introduce this new pediatric formulation of Orladeyo that could significantly reduce the treatment burden for children and families impacted by HAE,” Arnold said.