Sebetralstat for On-Demand Treatment of Mucosal Hereditary Angioedema Attacks in KONFIDENT-S.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Oral sebetralstat enabled rapid treatment of laryngeal and abdominal attacks of all severities, was well tolerated, and provided early symptom relief.