Ekterly pill may change how families treat HAE attacks in young children
This oral option could end treatment delays caused by fear of painful injections
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Children as young as 2 years may soon have access to the first-ever oral treatment for sudden hereditary angioedema (HAE) attacks.
New Phase 3 data from developer Kalvista Pharmaceuticals suggests that Ekterly (sebetralstat) is both safe and effective for young children, offering a needle-free alternative to the injectable therapies that currently dominate pediatric angioedema care.
The Phase 3 KONFIDENT-KID trial (NCT06467084), which completed enrollment a year ahead of schedule, is evaluating Ekterly’s safety and efficacy as an on-demand treatment for HAE attacks in 36 children, ages 2 to 11. While the therapy is approved in the U.S. for children as young as 12, younger children currently rely on injectable therapies. Because Ekterly can be taken by mouth, it may offer a more convenient on-demand option.
The findings were shared in a poster presentation, titled “On-demand Oral Sebetralstat for Hereditary Angioedema Attacks in Children Aged 2-11: Interim Analysis of KONFIDENT-KID,” at this year’s Global Angioedema Leadership Conference, held March 26-29 in Madrid, Spain.
A potential shift in HAE treatment
“Each update from KONFIDENT-KID continues to build compelling evidence that sebetralstat has the potential to transform the treatment paradigm for children living with HAE,” Ben Palleiko, CEO of Kalvista, said in a company press release. He noted that the rapid pace of enrollment and high attack treatment rate may signal a “meaningful shift” toward oral options.
Angioedema occurs when fluid builds up under the skin or mucous membranes, causing episodes of swelling that can affect various parts of the body. In HAE, genetic mutations lead to excessive bradykinin production, a molecule that widens blood vessels and causes fluid to leak into surrounding tissues, triggering swelling attacks.
“Managing HAE attacks in children remains particularly challenging, as currently available on-demand treatments rely on injections or intravenous [into-the-vein] infusions that can be painful, anxiety-inducing, and difficult to administer promptly at symptom onset,” said Emel Aygören-Pürsün, MD, a researcher at the University Hospital Frankfurt who presented the new interim data at the conference. “These barriers can contribute to treatment delays or avoidance, which may worsen outcomes.”
Ekterly is designed to be taken at the first sign of a swelling attack. The therapy works by blocking plasma kallikrein, an enzyme involved in bradykinin production, thereby lowering bradykinin levels and curbing the attack.
Ekterly was approved in the U.S. last year for use in adults and children, 12 and older, with HAE. The approval was supported by data from the Phase 3 KONDIFENT trial (NCT05259917), which showed that a single dose of Ekterly was sufficient to ease or fully resolve most swelling attacks in both adolescents and adults.
Data from the open-label extension study KONFIDENT-S (NCT05505916) demonstrated how much faster an oral pill can be utilized. Patients using injectable therapies often delay treatment by nearly four hours, whereas Ekterly users treated their symptoms in a median of 10 minutes, with most experiencing relief within about two hours. Ekterly was found to be safe and well tolerated. Early treatment is a cornerstone of international HAE guidelines, which recommend that therapies be administered as soon as possible to limit attack duration.
Positive interim results for young children
Interim results from the KONFIDENT-KID study, based on 172 attacks in 33 participants, showed a median time to treatment of 25 minutes, with 67% of attacks treated within the first hour. At the time of treatment, nearly 90% of attacks were mild or moderate.
The median time to symptom relief was 1.5 hours, while the time to complete attack resolution was 12 hours. The therapy was well tolerated, with no serious adverse events or reports of difficulty swallowing.
“The KONFIDENT-KID data demonstrate that children and caregivers were able to treat attacks early and achieve rapid symptom relief,” Aygören-Pürsün said. “An effective oral on-demand option has the potential to transform the treatment experience for children and families, reducing fear and burden while enabling early treatment of attacks.”
Kalvista expects to file for Ekterly’s label expansion this fall, with a potential launch in 2027. If approved, Ekterly would be the first oral on-demand therapy for children ages 2 to 11.
