KalVista Pharmaceuticals is expanding its regulatory efforts for sebetralstat, a novel oral treatment for hereditary angioedema (HAE), with submissions to regulatory authorities in the United Kingdom, Switzerland, Australia, and Singapore. These Marketing Authorization Applications (MAAs), filed via the Access Consortium framework, aim to address the unmet need for accessible on-demand treatment for HAE sufferers globally. If approved, sebetralstat would be the first oral medication for on-demand management of HAE attacks in adults and adolescents aged 12 and older, offering a significant improvement over existing intravenous or subcutaneous treatments. The U.S. FDA has set a Prescription Drug User Fee Act (PDUFA) date of June 17, 2025, for sebetralstat. The European Medicines Agency (EMA) has also validated the MAA.
Clinical Trial Data Supporting Sebetralstat
The MAAs are supported by data from the KONFIDENT phase 3 clinical trial, which demonstrated that sebetralstat significantly accelerated the onset of symptom relief compared to placebo (p<0.0001 for 300 mg, p=0.0013 for 600 mg). The ongoing KONFIDENT-S open label extension trial has shown a consistent safety and efficacy profile for sebetralstat, with a median time to beginning of symptom relief for laryngeal attacks of 1.3 hours. These results highlight the potential of sebetralstat to provide rapid relief from HAE attacks, which can be life-threatening depending on the affected location.
Pediatric Studies and Potential Expansion of Treatment Options
KalVista has also initiated the KONFIDENT-KID clinical trial, evaluating sebetralstat in children aged 2-11 years. This trial could position sebetralstat as the first oral on-demand therapy for this age group, pending approval. The pediatric oral disintegrating tablet (ODT) formulation used in the KONFIDENT-KID trial could provide a convenient and palatable option for young patients. Ben Palleiko, CEO of KalVista, stated, "We are building a global commercial presence to provide the greatest possible access to potentially the first oral on-demand treatment for this debilitating disease."
Addressing Unmet Needs in HAE Treatment
HAE is a rare genetic condition characterized by spontaneous and often painful swelling in various body parts, which can be life-threatening. Current on-demand treatments for HAE require either intravenous or subcutaneous administration, highlighting the need for more accessible treatment options like sebetralstat. Sebetralstat has received Fast Track and Orphan Drug Designations from the U.S. FDA and similar designations from the EMA, underscoring its potential to address a significant unmet medical need.
Trial Design and Patient Population
The KONFIDENT phase 3 clinical trial was a randomized, double-blind, 3-way crossover trial evaluating the safety and efficacy of sebetralstat 300 mg and 600 mg versus placebo for the on-demand treatment of HAE in adult and pediatric patients aged 12 years and older. The trial randomized a total of 136 HAE patients from 66 clinical sites across 20 countries. The KONFIDENT-S trial is an open label extension trial evaluating the long-term safety and efficacy of sebetralstat for on-demand treatment of HAE attacks in adults and pediatric patients aged 12 years and older with HAE Type I or Type II.
