KalVista Pharmaceuticals, Inc. announced positive results from the phase 3 KONFIDENT clinical trial demonstrating statistically and clinically significant efficacy of sebetralstat as oral on-demand therapy for hereditary angioedema (HAE). KONFIDENT was the largest and most representative trial ever conducted in HAE, and included adolescents, patients using long-term prophylaxis, and all attack severities and locations. The clinical trial met all primary and key secondary endpoints and demonstrated a favorable safety profile.

HAE attacks treated with both 300 mg and 600 mg of sebetralstat achieved the primary endpoint of beginning of symptom relief significantly faster than placebo (p<0.0001 for 300 mg, p=0.0013 for 600 mg). The median time to beginning of symptom relief was 1.61 hours with sebetralstat 300 mg (CI 1.28, 2.27), 1.79 hours with sebetralstat 600 mg (CI 1.33, 2.27) and 6.72 hours with placebo (CI 2.33, >12). Consistent with previous studies, sebetralstat was well-tolerated, with a safety profile similar to placebo.

There were no patient withdrawals due to any adverse event and no treatment-related serious adverse events (SAEs) were observed. Treatment-related adverse event rates were 2.3% for 300 mg sebetralstat, 2.2% for 600 mg sebetralstat, and 4.8% for placebo. Primary and key secondary endpoints were analyzed in a fixed, hierarchical sequence and adjusted for multiplicity.

Key secondary endpoints showed: Attacks treated with sebetralstat 300 mg or 600 mg achieved a significantly faster time to a reduction in attack severity from baseline, compared to placebo (p=0.0036 for 300 mg and p=0.0032 for 600 mg); Attacks treated with sebetralstat 300 mg or 600 mg demonstrated a significantly faster time to complete attack resolution, compared to placebo (p=0.0022 for 300 mg and p<0.0001 for 600 mg).