KalVista Pharmaceuticals presented new analyses of sebetralstat, an investigational oral plasma kallikrein inhibitor, at the Bradykinin Symposium 2024, reinforcing its potential as an effective on-demand treatment for hereditary angioedema (HAE) attacks. Data from Phase 2 and 3 trials, including the KONFIDENT-S open-label extension, demonstrated consistent efficacy and a safety profile comparable to placebo.
Rapid Symptom Relief
Key findings from the trials indicate that sebetralstat offers rapid symptom relief. The median time to treatment was 9 minutes for all attacks and 8 minutes specifically for laryngeal attacks. Patients experienced a median time to the beginning of symptom relief of 1.8 hours for all attacks and 1.3 hours for laryngeal attacks. These results suggest that sebetralstat could provide a significant benefit in managing HAE attacks, particularly those affecting the larynx, which can be life-threatening.
Addressing Unmet Needs in HAE Treatment
Currently approved on-demand treatments for HAE require intravenous or subcutaneous administration, which can lead to delays in treatment and injection-site reactions. Emel Aygören-Pürsün, MD, a leading investigator in the sebetralstat trials, noted that oral sebetralstat may remove these challenges and has a safety profile no different than placebo. The oral formulation of sebetralstat could improve patient compliance and enable earlier intervention during HAE attacks.
Consistent Efficacy and Safety
Paul Audhya, MD, MBA, Chief Medical Officer of KalVista Pharmaceuticals, emphasized the consistency of safety and efficacy observed across the entire clinical program for sebetralstat. Data presented at the symposium included pooled analyses of placebo-controlled trials, which corroborated the efficacy of sebetralstat and confirmed its favorable safety profile. In the KONFIDENT Phase 3 trial, the positive efficacy and safety results were consistent between European participants and the overall cohort, suggesting broad applicability of the treatment.
Implications for HAE Management
If approved, sebetralstat could transform the management of HAE by addressing critical gaps in the current standard of care. The availability of an effective oral treatment option may lead to earlier intervention, improved patient outcomes, and a better quality of life for individuals living with HAE. The FDA has accepted KalVista’s NDA for sebetralstat with a PDUFA goal date of June 17, 2025, and the company expects to file for approval in the UK, Japan, and other countries later in 2024.
