Investigational Plasma Kallikrein Inhibitor (Sebetralstat) Reduces Time to Relief from Hereditary Angioedema Attacks

In a Phase III, double-blind, threeway crossover trial, sebetralstat given on-demand for treatment of hereditary angioedema (HAE) attacks was shown to result in faster times to the start of symptom relief, reduction in attack severity and complete attack resolution than placebo treatment. Sebetralstat is an orally administered plasma kallikrein inhibitor currently being developed by KalVista Pharmaceuticals.

A total of 136 participants at least 12 years of age with type 1 or type 2 HAE were randomly assigned to take up to two oral doses of sebetralstat (300 mg or 600 mg) or placebo for an angioedema attack. The median time to the start of symptom relief was 1.61 and 1.79 hours, respectively, in the 300 mg and 600 mg sebetralstat groups, compared to 6.72 hours in subjects given placebo.

The median time to a reduction in attack severity was 9.27 and 7.75 hours in the 300 mg and 600 mg sebetralstat groups, while it exceeded 12 hours in the placebo group. The percentage of attacks with complete resolution within 24 hours was 42.5 percent and 49.5 percent with the 300 mg and 600 mg dosages, and 27.4 percent with placebo.

Sebetralstat and placebo exhibited similar safety profiles, and no serious adverse events related to the trial agents were reported. The study authors noted that sebetralstat’s oral route of administration could confer a therapeutic advantage over approved on-demand treatments for HAE attacks, whose parenteral route of administration is “associated with delays in treatment or withholding of therapy.”     ❖