Sebetralstat Provides Rapid, Sustained Relief for Breakthrough HAE Attacks Despite Prophylaxis: Study
Interim results from the KONFIDENT-S open-label extension study showed that oral sebetralstat 600 mg provided rapid relief for breakthrough hereditary angioedema (HAE) attacks in patients receiving long-term prophylaxis. Among 35 participants, 382 of 504 treated attacks showed a substantial residual disease burden despite prophylaxis. The median time from attack recognition to treatment was just 6 minutes, with symptom relief beginning at approximately 1.2–1.3 hours. In a post hoc analysis, the median time to the end of attack progression was 20.4 minutes, and 91% of attacks reached this stage within 4 hours. Benefits were consistent across different prophylactic therapies.
The study was published in The Journal of Allergy and Clinical Immunology by Tamar K. and colleagues. In order to analyze the safety and efficacy of the long-term use of sebetralstat orally (600 mg) for the treatment of acute swelling attacks, researchers conducted research on participants included in the multicenter KONFIDENT-S trial (NCT05505916).
The participants in the study were patients diagnosed with C1-inhibitor deficiency and taking lanadelumab, berotralstat, or C1-inhibitor as long-term prophylaxis. The endpoints for efficacy included the important time-to-event recovery outcomes such as time of recognizing the attack, time to start of attack alleviation, time to decrease in attack severity, and the time to full attack resolution at different body sites.
Key findings:
- In a study on 35 subjects taking background long-term prophylaxis, subjects had a mean of 1.7 ± 1.5 attacks per month and successfully managed 382 attacks in total using sebetralstat, which equates to 1.3 ± 1.1 sebetralstat-treated attacks per month.
- The median time for sebetralstat treatment following the recognition of the attack was extremely quick, averaging only 6 minutes (interquartile range [IQR], 1-40 minutes).
- The median time for sebetralstat to initiate relief of symptoms was 1.3 hours (IQR, 0.8-3.8 hours), the median time to decrease the severity of the attack was 4.2 hours (IQR, 1.3 to >12 hours), and the median time until full resolution of the attack was 14.8 hours (IQR, 4.6 to >24 hours).
- The efficacy of the sebetralstat treatment was extremely consistent irrespective of the type of background prophylaxis used.
In summary, the treatment of breakthrough attacks using sebetralstat was associated with quick relief of symptoms, reduced severity of attacks, and full resolution of the attacks irrespective of the mode of action of the underlying prophylaxis. The findings from this study confirm that sebetralstat is a flexible and convenient oral drug for the management of acute breakthrough attacks of hereditary angioedema patients. With quick relief of symptoms and without any additional toxicity, oral sebetralstat represents a significant advancement towards comprehensive management of hereditary angioedema.
Reference:
Kinaciyan, T., Aygören-Pürsün, E., Martinez-Saguer, I., Soteres, D. F., Honda, D., Manning, M. E., Wedner, H. J., Fukunaga, A., Kanarek, H. J., Kazumasa Ohmura, Melamed, I., El-Shanawany, T., Bouillet, L., Lumry, W. R., Riedl, M. A., Majed Koleilat, Geng, B., Isao Ohsawa, Bara, N., … Zanichelli, A. (2026). Sebetralstat for breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis in KONFIDENT-S. Journal of Allergy and Clinical Immunology Global, 5(5), 100750–100750. https://doi.org/10.1016/j.jacig.2026.100750
