Long-Term Safety and Effectiveness of Sebetralstat: Interim Analysis of KONFIDENT-S Open-label Extension.

BACKGROUND

Poor compliance with hereditary angioedema guidelines for on-demand treatment is common due to challenges with parenteral administration. Sebetralstat, an oral plasma kallikrein inhibitor, demonstrated faster times to beginning of symptom relief, reduction in attack severity, and complete resolution than placebo in the phase 3 KONFIDENT trial (NCT05259917).

OBJECTIVE

This analysis evaluated long-term safety and effectiveness of sebetralstat in KONFIDENT-S (NCT05505916), an ongoing, 2-year, open-label extension study.

METHODS

Enrolled participants aged ≥12 years with hereditary angioedema due to C1-inhibitor deficiency administered sebetralstat 600 mg for each attack, as early as possible, regardless of severity or location. The primary outcome was incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes were times to beginning of symptom relief, reduction in severity, and complete resolution.

RESULTS

At data cutoff (January 31, 2024), 84 participants (mean age: 35.9 years; 14.3% <18 years; 64.3% female) treated 640 attacks with sebetralstat (84% of total attacks); the median (interquartile range [IQR]) number of attacks per participant was 5 (2-8). The median (IQR) time from attack onset to treatment was 9 (1-69) minutes. Baseline severity was as follows: 30.0% mild, 43.3% moderate, and 25.0% severe or very severe. Treatment-related TEAEs occurred in 8 participants (9.5%); none were serious. The median time to beginning of symptom relief (allowing for missing data entries between consecutive time points) was 1.68 (0.79-3.89) hours, to reduction in severity 6.57 (1.61 to >12) hours, and to complete attack resolution 21.02 (7.22 to >24) hours. No evidence of a diminished response over repeated treatments of attacks was observed.

CONCLUSIONS

Oral sebetralstat enabled compliance with treatment guidelines. No new safety signals were observed, and effectiveness for repeated attacks was consistent with the KONFIDENT trial results.