KalVista announces publication of data from Phase 3 KONFIDENT trial

KalVista Pharmaceuticals announced that late-breaking data from the pivotal phase 3 KONFIDENT trial and open label KONFIDENT-S extension trial evaluating the efficacy and safety of sebetralstat were presented as late-breaking presentations at the European Academy of Allergy and Clinical Immunology Congress 2024. The results of KONFIDENT were simultaneously published in The New England Journal of Medicine. As presented and published, the KONFIDENT trial met its primary and key secondary endpoints and demonstrated a safety profile no different from placebo. Median time from attack onset to treatment was 41 min with 55.7% of participants treating in less than 1 hour; 42.8% of attacks treated when still mild. Primary endpoint: Time to beginning of symptom relief was significantly faster than placebo; Median time to beginning of symptom relief was 1.61 hours with sebetralstat 300 mg, 1.79 hours with sebetralstat 600 mg, and 6.72 hours with placebo. Key secondary endpoints: Significantly faster time to a reduction in attack severity from baseline compared to placebo; Significantly faster time to complete attack resolution compared to placebo; Primary and key secondary endpoints were analyzed in a fixed, hierarchical sequence and adjusted for multiplicity. Subgroup analyses showed a consistency of treatment effect in among attacks regardless of attack severity, attack location, use of long-term prophylaxis, or geography. The safety of sebetralstat at both dose levels was no different than placebo. There were no patient withdrawals due to any adverse events and no treatment-related serious adverse events were observed. Treatment-related adverse event rates were 2.3% for 300 mg sebetralstat, 3.2% for 600 mg sebetralstat, and 4.8% for placebo. Phase 3 KONFIDENT-S Open-Label Extension Trial Interim Results: 112 participants enrolled; 15.2% aged 12-less than18 years, 81.3% aged 18-less than65 years, and 2.7% aged greater than or equal to65 years; 68.8% receiving on-demand treatment only; 31.3% receiving stable long-term prophylaxis; 649 attacks treated with sebetralstat; median 5.0 attacks treated per participant; Median time from attack onset to treatment was 9 minutes; Median time to beginning of symptom relief was 1.8 hours; Median times to reduction in attack severity and complete attack resolution were consistent with results in the KONFIDENT Trial. KONFIDENT and KONFIDENT-S are the first and only clinical trials ever to include complete symptom relief as an endpoint; all other trials use near-complete relief, which is a much lower standard that does not capture the entire attack sequence in the same manner. Laryngeal attack subgroup, median time to beginning of symptom relief was 1.3 hours.