From injectable to oral: Sebetralstat as a first-in-class plasma kallikrein inhibitor and the evolving paradigm of hereditary angioedema treatment

Hereditary angioedema (HAE) is a rare inherited condition marked by recurrent swelling episodes involving the skin and submucosal tissues. The underlying mechanism is bradykinin - driven vascular leakage, most commonly arising from deficiency or functional i mpairment of C1 esterase inhibitor and the resulting loss of control over the kallikrein – kinin cascade. While several effective options are available for both acute management and prophylaxis, the majority rely on injectable administration, which can compl icate timely treatment and negatively influence long - term adherence. Sebetralstat (Ekterly) is the first orally administered, FDA - approved on - demand therapy for acute HAE attacks in patients aged 12 years and older. By selectively inhibiting plasma kallikr ein, it limits downstream bradykinin production and reduces edema formation. In the Phase 3 Konfident trial, sebetralstat was associated with faster symptom resolution, attenuation of attack severity, and a safety profile similar to that observed with plac ebo. The availability of an oral, self - administered option represents a meaningful shift in HAE care, allowing earlier intervention and offering practical benefits for patients in day - to - day disease management.