On-demand sebetralstat effective for hereditary angioedema attacks in larynx
Key takeaways:
- 1.9% of hereditary angioedema attacks involved the larynx, which could be fatal.
- Patients took sebetralstat 11.5 minutes after these attacks began.
- 96% of patients saw relief after one dose of sebetralstat.
SAN DIEGO — Patients with hereditary angioedema whose attacks impacted their larynx experienced on-demand relief within 1.29 hours with oral sebetralstat, preventing potentially fatal outcomes, according to an abstract presented here.
Patients could swallow the biologic despite the swelling in their throat, Jonathan A. Bernstein, MD, FAAAAI, FACAAI, FACP, adjunct professor, University of Cincinnati College of Medicine, said at the 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress.
“This one is a kallikrein inhibitor,” Bernstein told Healio. “This is very similar to some of the existing treatments, except the pharmacokinetics lend it to use in acute settings, so it works quickly. That’s the advantage.”
More than 50% of patients with hereditary angioedema (HAE) experience an attack that involves their throat, which could be fatal within 10 minutes of onset without prompt administration of treatment, at least once in their lives, the researchers said.
Current on-demand treatment for attacks must be administered parenterally, the researchers continued, which may delay or prevent care. Sebetralstat (KalVista Pharmaceuticals) is administered orally and does not require any injections, which “makes it very convenient,” Bernstein said.
“This is first in class for acute on-demand,” he said.
In this interim analysis of findings from the KONFIDENT-S study, researchers examined sebetralstat and its tolerability, safety and effectiveness as an on-demand treatment for HAE attacks involving the larynx.
KONFIDENT-S included 134 patients (median age, 35 years; 64.9% female; 73.9% white) aged 12 years and older with HAE. Also, 93.3% had type 1 HAE, 73.9% used on-demand treatment only and 26.1% used on-demand treatment with long-term prophylaxis.
These patients experienced 1,706 attacks between Oct. 21, 2022, and Sept. 14, 2024, including 32 attacks (1.9%) among 16 patients (median age, 44.5 years; 62.5% female; 81.3% white) that involved the larynx.
All the patients with attacks involving the larynx had type 1 HAE. Additionally, 56.3% used on-demand treatment only, and 43.8% used on-demand treatment and long-term prophylaxis.
The attacks that involved the larynx included seven (21.9%) that were considered mild, 15 (46.9%) that were considered moderate, and nine (28.1%) that were considered severe or very severe.
Patients were told to treat themselves with 600 mg of sebetralstat as soon as they began experiencing an attack. If their laryngeal symptoms got worse after taking the sebetralstat, patients were told to use conventional on-demand treatment.
“There was no trouble swallowing the pill during the attack, so they could get it down to where it needed to be,” Bernstein told Healio.
Median times from the onset of attack to treatment with sebetralstat included 10 minutes for the full cohort and 11.5 minutes for the attacks involving the larynx.
Patients whose attacks involved the larynx began experiencing symptom relief at a median of 1.29 hours and reductions in attack severity at a median of 4.25 hours. Attacks were completely resolved at a median of 12.69 hours.
“That’s reasonable for comparing other treatments that are used for on-demand,” Bernstein said.
The researchers defined the beginning of symptom relief as a Patient Global Impression of Change rating of “A Little Better” or higher for two or more consecutive time points within 12 hours.
Reductions in attack severity were defined as a decrease of one level or more on the Patient Global Impression of Severity (PGI-S) at two or more consecutive time points within 12 hours. Complete resolution was defined as a PGI-S rating of none within 24 hours.
“They have many different parameters they were looking at,” Bernstein said.
After four of these attacks (12.5%), patients administered a second dose of sebetralstat within 12 hours. After three attacks (9.4%), patients administered conventional treatment within 12 hours, with an additional attack addressed with conventional treatment without a timeframe reported.
Two of these administrations of conventional treatment occurred after a single dose of sebetralstat. One of these patients used conventional treatment 1 minute after taking sebetralstat in response to a very severe attack. The patient who used conventional treatment after two doses of sebetralstat did so 11.7 hours after the first sebetralstat dose.
In 96% of the patients with an attack involving the larynx, symptom relief followed a single dose of sebetralstat.
“Most of the attacks achieved symptom relief without additional administrations,” Bernstein said.
Seven patients with attacks involving the larynx (43.8%) experienced treatment-emergent adverse events, including two that were serious and three that were severe. Only one of these events was considered related to treatment, involving grade 2 nausea and vomiting, but it was neither serious nor severe. Only one event led to permanent discontinuation as well, but it also was neither serious nor severe.
“It was well tolerated,” Bernstein said.
Based on these findings, which Bernstein called consistent with findings for on-demand treatment for attacks occurring in other parts of the body, the researchers called sebetralstat effective and well tolerated in treating HAE attacks involving the larynx.
“This is very important, obviously, because this is a thing that leads to death,” Bernstein said, adding that he and his colleagues have “confidence that it works.”
Bernstein also said that sebetralstat’s oral administration may improve adherence to on-demand treatment.
“We encourage patients to carry treatment with them. Sometimes, they don’t always carry it,” he said. “We hope that with oral, they’ll be able to be more adherent.”
Further, Bernstein said that patients have a good sense of when to use treatment.
“Patients with HAE know what’s going on with their body. They start feeling a fullness,” he said. “They’re going to treat. They should treat. You want to err on the side of commission than omission.”