A recent study found that 42.5% of hereditary angioedema attacks treated with a 300 mg dose of oral sebetralstat achieved complete resolution within 24 hours, compared to 49.5% for the 600 mg dose, and 27.4% for the placebo (P=.002 and P<.001, respectively).

The phase 3 trial, published in the New England Journal of Medicine, evaluated the efficacy and safety of oral sebetralstat for the on-demand treatment of hereditary angioedema (HAE) attacks. The double-blind, three-way crossover trial included 136 participants aged 12 years and older with type 1 or type 2 HAE. Participants were randomized to receive either 300 mg or 600 mg of sebetralstat or a placebo during an angioedema attack.

The primary endpoint was the time to the beginning of symptom relief, defined as a rating of "a little better" on the Patient Global Impression of Change scale at two or more consecutive time points within 12 hours. Secondary endpoints included reduction in attack severity and complete attack resolution within 24 hours.

Results indicated that both doses of sebetralstat were significantly more effective than placebo. The median time to symptom relief was 1.61 hours for the 300 mg dose and 1.79 hours for the 600 mg dose, compared to 6.72 hours for the placebo (P<.001 and P=.001, respectively). The median time to reduction in attack severity was 9.27 hours for the 300 mg dose and 7.75 hours for the 600 mg dose, versus over 12 hours for the placebo (P=.004 and P=.003, respectively).

Sebetralstat and placebo exhibited similar safety profiles, with no serious adverse events related to the trial agents reported.

The study suggests that sebetralstat may offer an effective oral treatment option for HAE attacks, demonstrating faster times to symptom relief and attack resolution compared to placebo.

The study was funded by KalVista Pharmaceuticals.