International guideline recommends sebetralstat as first-line acute therapy for adolescents with hereditary angioedema

A newly published international guideline on the diagnosis and management of pediatric hereditary angioedema (HAE) provides updated, evidence-based recommendations for children and adolescents with HAE due to C1 inhibitor deficiency (HAE-C1INH), including a strong recommendation for sebetralstat as a first-line option for acute treatment in adolescents 12 years and older.^1,2

The guideline, developed by an international steering committee, task force, and the Hereditary Angioedema Working (HAWK) Group, was published in Allergy, the official journal of the European Academy of Allergy and Clinical Immunology. It addresses age-specific considerations in diagnosis, acute treatment, short-term prophylaxis, and long-term prophylaxis for pediatric patients.¹

Emphasis on early diagnosis and age-specific management

HAE-C1INH is a rare, autosomal dominant disorder characterized by recurrent, unpredictable episodes of subcutaneous and submucosal swelling. Attacks often begin in childhood, with a mean age of first attack around aged 10 years, and may worsen during puberty. Upper airway angioedema can be life-threatening if not promptly treated.

The guideline recommends that clinicians consider HAE in pediatric patients with recurrent peripheral edema, upper airway edema, or unexplained abdominal pain, regardless of family history, and perform biochemical testing with C4 and C1 inhibitor antigenic and functional levels. Two congruent test results are required to confirm or exclude HAE-C1INH.

Screening of first-degree relatives and early newborn evaluation in families with known HAE are also recommended to facilitate timely diagnosis and access to treatment.

First-line acute therapy in adolescents includes sebetralstat

Acute treatment aims to reduce attack severity and duration and to prevent mortality. The guideline emphasizes that treatment should be administered as early as possible and be available at all times, including at home and during school or travel.

For adolescents 12 years or older, the guideline recommends ecallantide, icatibant, intravenous plasma-derived C1 inhibitors, intravenous recombinant human C1 inhibitors, or sebetralstat as first-line therapy for acute treatment of angioedema attacks.²

KalVista Pharmaceuticals announced February 18, 2026, that Ekterly (sebetralstat) received a strong recommendation as a first-line therapy for adolescents 12 years and older. According to the company, the recommendation was based on high-quality clinical evidence demonstrating consistent efficacy, rapid symptom relief, and a favorable safety profile.²

“We are encouraged to see this international guideline reflect the progress the HAE community has made toward more patient-centered care, particularly for adolescents,” said Paul Audhya, MD, MBA, chief medical officer of KalVista. “The first-line recommendation for Ekterly so soon after becoming commercially available underscores the strength of our clinical data and reinforces the importance of ensuring patients have immediate access to effective on-demand therapy. 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.”

Sebetralstat is currently approved in the United States, European Union, United Kingdom, Switzerland, Australia, Singapore, and Japan for the treatment of acute HAE attacks in patients 12 years and older. It is the first and only oral on-demand treatment option in this population.

Addressing treatment delays in adolescents

The guideline underscores the importance of early intervention, noting that earlier treatment is associated with shorter and less severe episodes. Real-world data cited in the press release indicate that adolescents historically delayed treatment by nearly 8 hours on average, often due to anxiety or challenges associated with injectable therapies.

To support timely treatment, the guideline recommends that pediatric patients have on-demand therapy available anytime and anywhere, that clinicians consider treatment of all attacks, and that patients maintain sufficient supply to treat at least 2 attacks, even when receiving long-term prophylaxis.

“While general protocols have existed for many years, these new recommendations recognize that children require care tailored to their unique needs to manage this rare and potentially life-threatening genetic condition,” said Mauro Cancian, MD, PhD, head of the Allergy Division at the University of Padua in Padova, Italy. “HAE presents distinct physiological and psychological hurdles, particularly in adolescents, from puberty-driven flare-ups to the trauma of frequent injections. 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.”

Ongoing pediatric development

KalVista is advancing the KONFIDENT-KID trial (NCT06467084) evaluating sebetralstat in children aged 2 to 11 years and anticipates submitting a new drug application for this age group in the third quarter of 2026.

The guideline authors emphasize that management of pediatric HAE should occur in specialized comprehensive care centers and include education for patients, caregivers, schools, and community providers to ensure rapid recognition and treatment of attacks.

Together, the updated recommendations aim to standardize pediatric HAE care globally and improve access to age-appropriate, evidence-based treatment options.

References

1. Farkas H, Martinez-Saguer I, Bork K, et al. International guideline on the diagnosis and management of pediatric patients with hereditary angioedema. Allergy. Published online January 30, 2026. doi:10.1111/all.70207
2. KalVista Pharmaceuticals announces inclusion of Ekterly (sebetralstat) as a first-line therapy for adolescents 12 and older in international pediatric HAE guideline. New release. KalVista. February 18, 2026. Accessed February 18, 2026. https://www.businesswire.com/news/home/20260218359223/en/KalVista-Pharmaceuticals-Announces-Inclusion-of-EKTERLY-sebetralstat-as-a-First-Line-Therapy-for-Adolescents-12-and-Older-in-International-Pediatric-HAE-Guideline