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The following is a summary of “Indirect treatment comparison of oral sebetralstat and intravenous recombinant human C1 esterase inhibitor for on-demand treatment of hereditary angioedema attacks,” published in the March 2025 issue of Allergy, Asthma & Clinical Immunology by Li et al. 

On-demand treatment for hereditary angioedema aims to stop attack progression. A total of 4 treatments were approved, including (ecallantide, icatibant, recombinant human C1 esterase inhibitor [rhC1INH], and plasma-derived C1INH) and sebetralstat. 

Researchers conducted a retrospective study using an indirect treatment comparison (ITC) to assess efficacy and safety without head-to-head trials. 

They conducted a systematic literature review and feasibility assessment, identifying one rhC1INH trial (NCT01188564) with comparable efficacy data. They used Bayesian fixed-effects network meta-analysis models to compare efficacy and safety (NCT01188564, NCT00225147, NCT00262301). They performed a matching-adjusted indirect comparison (MAIC), adjusting for baseline attack severity and demographic characteristics. 

The results showed no significant differences in time to symptom relief between sebetralstat 300 mg and rhC1INH 50 IU/kg (hazard ratio (HR) [95% credible interval], 0.96 [0.42–2.15] to 1.19 [0.58–2.45]). After adjusting for baseline attack severity, MAIC showed numerically favorable results for sebetralstat, regardless of demographic matching. The fixed-effects model found no significant differences in treatment-related treatment-emergent adverse events. Sensitivity analyses returned consistent results. 

Investigators found no significant differences in time to symptom relief and treatment-related treatment-emergent adverse events between sebetralstat and rhC1INH.

Source: aacijournal.biomedcentral.com/articles/10.1186/s13223-025-00955-6