# Sebetralstat for On‐Demand Treatment of Mucosal Hereditary Angioedema Attacks in KONFIDENT‐S

## TL;DR

Sebetralstat, an oral treatment, was found to be effective and well-tolerated for managing mucosal hereditary angioedema attacks, providing rapid symptom relief.

## Contribution

This study evaluates sebetralstat's safety and effectiveness for on-demand treatment of mucosal HAE attacks in a real-world setting.

## Key findings

- Sebetralstat provided rapid symptom relief for laryngeal and abdominal HAE attacks with median times under 1.3 hours.
- Most attacks achieved symptom relief with a single dose of sebetralstat within 12 hours.
- The treatment was well-tolerated with low incidence of adverse events.

## Abstract

Hereditary angioedema (HAE‐C1INH) attacks involving mucosal tissue may progress rapidly and often lead to substantial morbidity. Severe laryngeal attacks can be fatal without prompt administration of on‐demand treatment. This prespecified interim analysis evaluated the safety and effectiveness of sebetralstat in laryngeal and abdominal attacks in the ongoing, 2‐year, open‐label extension KONFIDENT‐S study (NCT05505916).

Eligible participants ≥ 12 years with HAE‐C1INH self‐administered sebetralstat 600 mg film‐coated tablets with an optional second dose after 3 h, if warranted. Primary outcome: incidence of treatment‐emergent adverse events (TEAEs). Secondary outcomes: times to beginning of symptom relief, reduction in severity, and complete resolution.

At data cutoff (Sep 14, 2024), 32 laryngeal (16 participants) and 533 abdominal only attacks (102 participants) were treated with sebetralstat. Seven (43.8%) participants with laryngeal attacks experienced 14 TEAEs whereas 36 (35.3%) participants with abdominal attacks experienced 91 TEAEs. No difficulty swallowing sebetralstat was reported. Median (IQR) time to treatment: 11.5 min (1.0–34.0) and 20.0 min (1.0–61.0) for laryngeal and abdominal attacks, respectively; time to beginning of symptom relief: 1.29 h (0.76–3.02) and 1.27 h (0.76–3.54); reduction in attack severity: 4.25 h (1.22 to > 12) and 3.52 h (1.26 to > 12); complete attack resolution: 12.69 h (5.11 to > 24) and 15.17 h (4.46 to > 24). Most mucosal attacks that achieved beginning of symptom relief within 12 h did so with a single dose of sebetralstat (laryngeal: 96.0%; abdominal: 95.8%). Conventional on‐demand treatment was administered within 12 h for 3 (9.4%) laryngeal and 43 (8.1%) abdominal attacks.

Oral sebetralstat enabled rapid treatment of laryngeal and abdominal attacks of all severities, was well tolerated, and provided early symptom relief.

Mucosal hereditary angioedema attacks may progress rapidly and often lead to substantial morbidity. In the ongoing, international, 2‐year KONFIDENT‐S open‐label extension study, sebetralstat enabled early treatment and was generally well‐tolerated and effective in treating both laryngeal and abdominal HAE attacks.