D1.258 - First real-life experiences with Sebetralstat as oral on-demand treatment for acute HAE attacks documented in a global angioedema disease registry

Background: Hereditary angioedema (HAE) is a rare, inherited, potentially life-threatening disease characterized by unpredictable swellings attacks, most commonly caused by C1 inhibitor (C1INH) deficiency (HAE-C1INH). To date, on-demand treatments for acute attacks have been limited to injectable therapies which may be associated with administration–related burden and delayed treatment initiation. Sebetralstat, a plasma kallikrein inhibitor, was recently approved as the first oral on-demand treatment for acute HAE attacks in patients aged 12 years and older and has been available in Germany since November 2025. The recommended dose is a 300 mg tablet of Sebetralstat, a second dose may be taken 3 hours after the first dose if response is inadequate.

Methods: As of 05 January 2026, clinical data of patients using Sebetralstat for the treatment of acute attacks were extracted from the global Chronic Angioedema Registry (CARE).

Results: Two 31-year German female patients with HAE-C1INH treated at Charité - Universitätsmedizin Berlin switched their on-demand treatment from Icatibant or C1INH to Sebetralstat due to easier administration and the possibility of earlier treatment initiation. Treatment of three attacks was documented. Patient 1 experienced an abdominal attack, which she treated 1 hour and 15 minutes after recognition of initial symptoms; the patient could maintain daily activities, and no second dose was required. Patient 2 treated two swelling attacks. The first cutaneous attack was treated 1 minute after symptom recognition; the patient could maintain daily activities, and no second dose was required. The second abdominal attack was treated 5 minutes after symptom onset; daily activities remained unaffected, a second dose was required, and no further information is available. For all three attacks, both patients achieved ≥90% symptom improvement within 4 hours after medication intake. Both patients reported no side effects.

Conclusion: To our knowledge, this is the first real-world, single-center experience with an oral on-demand treatment for HAE attacks documented in a global angioedema registry. Real-world data fromthe two patients align with Sebetralstat efficacy and safety results from pivotal trials and underscore its potential to address unmet needs in HAE, including early attack treatment and reduced treatment burden.

Acknowledgments: We thank the CARE office, CARE management team and CARE Steering Committee for the establishment of the angioedema disease register as well as the patientsfor giving consent to present the clinical data. CARE receives financial funding support from BioCryst, CSL Behring, KalVista Pharmaceuticals, Pharvaris, Takeda, Otsuka and IntelliaTherapeutics.

The authors independently prepared this abstract. KalVista Pharmaceuticals was not involved in its conception, analysis, or drafting.

Ethics Statement: The Chronic Angioedema Registry was approved by the local ethics committee at Charité –Universitätsmedizin Berlin (EA2/145/23), and all data collection was conducted in accordance with ethical guidelines.