D3.448 - Use of Sebetralstat as Short-term Prophylaxis for Patients with Hereditary Angioedema: Results from the KONFIDENT-S Study

For people living with hereditary angioedema (HAE), guidelines recommend short-term prophylaxis (STP) with intravenous (IV) human plasma-derived concentrate C1-inhibitor (pdC1INH) before medical, surgical, or dental procedures to reduce the risk of triggering an HAE attack. However, obtaining and administering IV pdC1INH is often challenging and burdensome to patients. Sebetralstat was recently approved in Europe as the first oral on-demand treatment for HAE attacks. The potential for sebetralstat as an alternative STP regimen is being evaluated as part of the KONFIDENT-S 2-year open-label extension. 

In consultation with their study physician, participants enrolled in KONFIDENT-S administered 3 doses of 600 mg sebetralstat, with the first dose taken 1h prior to a planned procedure, a second dose 6-8h after the first dose, and a third dose 6-10h after the second dose. Effectiveness was assessed by the number of procedures that did not trigger an HAE attack within 24h after the start of the procedure. Participants using long-term prophylaxis (i.e., pdC1INH, lanadelumab, berotralstat) were ineligible to use sebetralstat for STP during the study.

As of September 30, 2025, 16 of 136 participants (11.8%) enrolled in KONFIDENT-S from 11 countries (mean age 34.6 years, 2 adolescents, 62.5% female, 68.8% White) used sebetralstat as STP for 44 procedures, including 33 dental procedures, 7 endoscopies/colonoscopies, and 4 additional procedures (dermal filler injection, lipoma excision, papilloma excision, eyebrow microblading). For 36 procedures in which all three doses of sebetralstat were administered, 0 attacks occurred within 24h. For 6 procedures, only the first two doses are sebetralstat were administered and 1 attack (16.7%) occurred within 24h of a dermal filler injection. The attack was mild in severity and occurred in the head/face/neck. A single dose of sebetralstat was administered for 2 procedures, with 1 attack (50%) occurring within 24h of a colonoscopy. The participant only administered the first dose of sebetralstat (prior to the procedure); attack severity and location were not reported. 

Preliminary data from KONFIDENT-S suggests that sebetralstat was an effective oral STP option for patients undergoing routine medical or dental procedures. When ≥2 doses were administered (n=42/44), the attack rate within 24h was 2.3%. These findings support the continued evaluation of sebetralstat as an alternative STP regimen.