KalVista Pharma's Sebetralstat Phase 3 Data Published in NEJM, Shows Potential for Hereditary Angioedema Treatment Transformation

In a significant development for the treatment of hereditary angioedema (HAE), KalVista Pharmaceuticals, Inc. has announced promising results from its pivotal phase 3 KONFIDENT trial and the ongoing KONFIDENT-S open-label extension trial. These findings were presented at the European Academy of Allergy and Clinical Immunology Congress 2024 and published in The New England Journal of Medicine. The trials assessed the efficacy and safety of sebetralstat, a novel oral therapy for on-demand HAE treatment.

The KONFIDENT trial, which enrolled 136 adult and adolescent HAE patients from 66 clinical sites across 20 countries, has shown remarkable efficacy. The median time from the onset of an attack to treatment was 41 minutes, with more than half of the participants treating their attacks in less than an hour. Sebetralstat significantly reduced the time to the beginning of symptom relief compared to a placebo, with median times of 1.61 hours for the 300 mg dose and 1.79 hours for the 600 mg dose, as opposed to 6.72 hours for the placebo.

Key secondary endpoints also highlighted sebetralstat’s effectiveness. The time to reduction in attack severity and complete attack resolution was markedly faster than with a placebo. Importantly, these results were consistent across various attack severities and locations, and regardless of long-term prophylaxis use. Safety data showed that sebetralstat was comparable to the placebo, with low rates of treatment-related adverse events and no serious adverse events reported.

Dr. Paul Audhya, KalVista’s Chief Medical Officer, emphasized the significance of these findings, noting that sebetralstat could become the first new oral therapy for HAE in over a decade, providing a much-needed on-demand treatment option for patients. The trial results suggest that sebetralstat offers rapid symptom relief with a favorable safety profile.

Interim results from the KONFIDENT-S trial further support these findings. This open-label extension study has enrolled 112 participants, with a median treatment time of just 9 minutes from attack onset. The median time to the beginning of symptom relief was 1.8 hours, consistent with the KONFIDENT trial results. Additionally, in a subgroup of patients experiencing laryngeal attacks, the median time to symptom relief was 1.3 hours.

Dr. Danny Cohn, the principal investigator for the KONFIDENT phase 3 trial, highlighted the potential of sebetralstat to meet the long-standing need for an effective oral on-demand treatment. The trial results demonstrated consistent efficacy regardless of attack severity or location, reinforcing the drug's potential to transform HAE management.

KalVista Pharmaceuticals plans to submit a new drug application for sebetralstat to the U.S. FDA in June 2024, with anticipated approvals in the UK, Europe, and Japan later in the year. The company’s CEO, Ben Palleiko, expressed gratitude to the trial participants and emphasized the promising future of sebetralstat in providing rapid and effective relief for HAE patients.

Sebetralstat, discovered by KalVista, is an investigational oral plasma kallikrein inhibitor designed for on-demand treatment of HAE. It has received Fast Track and Orphan Drug designations from the U.S. FDA and an approved Pediatric Investigational Plan from the European Medicines Agency.

HAE is a rare genetic disease characterized by painful and potentially life-threatening swelling attacks due to a deficiency or dysfunction in the C1 esterase inhibitor protein. Current on-demand treatment options for HAE typically require intravenous or subcutaneous administration, highlighting the need for an effective oral alternative like sebetralstat.

KalVista Pharmaceuticals, a global company focused on developing oral medicines for unmet medical needs, continues to advance sebetralstat towards regulatory approval and hopes to significantly improve the quality of life for HAE patients worldwide.