Ekterly use urged for kids with HAE 12 and older in new international guideline
Tablets recommended as first treatment for swelling attacks in adolescents
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A new international guideline recommends Ekterly (sebetralstat), Kalvista Pharmaceuticals’ approved oral therapy for hereditary angioedema (HAE), as a first-line option for timely, on-demand resolution of HAE swelling attacks in children ages 12 and older.
The committee behind these new pediatric guidelines stated in a study recommendation that adolescents with HAE “should be encouraged to take an active role in their own care.”
The “International Guideline on the Diagnosis and Management of Pediatric Patients with Hereditary Angioedema” — which contains 46 recommendations, including greater self-administration, for treating children and adolescents with HAE — was published in the journal Allergy. The recommendations were reviewed and voted on at a workshop held last year in Budapest, Hungary, and supported in part by Kalvista.
“Self-administration confers generic benefits, [including] … improved adherence to medication regimens in the longer term [and] enhancing independence and autonomous self-care,” the guideline states.
Ekterly is the only on-demand treatment for HAE available as oral tablets. According to Kalvista, the medication offers a more convenient alternative to other approved treatments that must be injected under the skin or into the bloodstream. Its unique formulation makes it easier for younger patients to follow the new recommendations, helping them treat an attack as soon as symptoms become evident.
“As the first and only oral on-demand treatment for HAE, Ekterly uniquely enables guideline-aligned care by supporting early intervention and simplifying self-administration, empowering adolescents 12 and older to treat at the earliest recognition of an attack,” Paul Audhya, MD, Kalvista’s chief medical officer, said in a company press release.
HAE is caused by genetic mutations, usually inherited, that result in excessive production of bradykinin, a molecule that widens blood vessels. This causes fluid to leak into the deeper layers of the skin or mucous membranes, triggering the episodes of swelling characteristic of angioedema.
On-demand Ekterly works to prevent worsening swelling in HAE
Ekterly works by inhibiting the activity of kallikrein, an enzyme involved in bradykinin production. By blocking kallikrein, Ekterly reduces the amount of bradykinin produced during an HAE attack. This is expected to shorten an attack’s duration and prevent worsening swelling.
The recommendation to use this on-demand treatment as a first-line option was based on Phase 3 clinical trial data from KONFIDENT (NCT05259917) and its open-label extension KONFIDENT-S (NCT05505916). The now-completed study and its extension also supported the approval of Ekterly in the U.S. and the European Union and Switzerland last year for patients ages 12 and older.
The new guideline aims to improve care for pediatric HAE patients.
“We are encouraged to see this international guideline reflect the progress the HAE community has made toward more patient-centered care, particularly for adolescents,” Audhya said. “The first-line recommendation for Ekterly so soon after becoming commercially available underscores the strength of our clinical data.”
The guideline stresses that early treatment is linked to better outcomes. When treatment begins soon after symptoms appear, attacks tend to be shorter and less severe. However, real-world data show that adolescents often delay treatment — sometimes by about eight hours — largely due to anxiety or difficulty with injectable medications.
To address this problem, the guideline recommends that children and adolescents should always have on-demand treatment available wherever they are. It also recommends keeping enough supply to treat at least two attacks, even if they are on preventive treatment, and having medication ready during possible triggering events such as medical, dental, or surgical procedures.
“Treatment outcomes have been shown to improve with earlier treatment administration as compared to later-stage treatment,” the guideline’s authors wrote. “Early treatment is supported by home treatment or self-injection after appropriate training,” adding that, “acute treatment should be immediately available under every circumstance, including at home, kindergarten, school, and while traveling.”
These new recommendations recognize that children require care tailored to their unique needs.
Another recommendation is to create an action plan for the acute treatment of HAE in pediatric patients. Such plans should take into account the type of medication available as well as the preferences of the individual patient and caregivers. All attacks should be treated, and it is recommended that they be treated at home and as early as possible.
“These new recommendations recognize that children require care tailored to their unique needs,” said Mauro Cancian, MD, PhD, head of the allergy division at the University of Padua in Italy. “By moving beyond a ‘one-size-fits-all’ approach, the guidelines provide a clear framework for care that supports not only rapid life-saving treatment, but also a child’s long-term health and emotional well-being.”
According to Kalvista, the guideline was created by an international steering committee, a taskforce, and the Hereditary Angioedema Working (HAWK) group.
Kalvista now developing formulation that dissolves on the tongue
Ekterly is already being marketed in the U.S. and Germany, with more launches planned.
Kalvista is now working to advance a sebetralstat formulation that dissolves on the tongue.
The developer ran a Phase 3 clinical trial, dubbed KONFIDENT-KID (NCT06467084), that tested the formulation’s safety and effectiveness in children with HAE ages 2 to 11. Building on positive data from that trial, the company plans to file an application seeking approval of sebetralstat. If approved, it could become the first oral on-demand treatment for younger patients with HAE.
