KalVista Pharmaceuticals, Inc. (NASDAQ: KALV) has announced that the European Medicines Agency (EMA) has validated their Marketing Authorization Application (MAA) for sebetralstat, an investigational oral plasma kallikrein inhibitor intended for the on-demand treatment of hereditary angioedema (HAE). The application will now undergo review by the EMA’s Committee for Medicinal Products for Human Use (CHMP), covering all 27 EU member states and EEA countries.
KalVista’s CEO, Ben Palleiko, noted that this validation moves them closer to making sebetralstat available globally. If approved, it would be the first oral on-demand treatment for HAE in Europe, potentially becoming a key treatment option for the condition.
The MAA is supported by data from the KONFIDENT phase 3 trial and the KONFIDENT-S extension trial. In the KONFIDENT trial, both 300 mg and 600 mg doses of sebetralstat showed significantly faster symptom relief compared to placebo (p<0.0001 for 300 mg and p=0.0013 for 600 mg) and had a safety profile similar to placebo. The KONFIDENT-S trial demonstrated that sebetralstat allowed for earlier attack treatment, with a median time from attack onset to treatment of 9 minutes and effective symptom relief for laryngeal attacks within 1.3 hours.
Recent findings from the KONFIDENT trial were published in The New England Journal of Medicine, and data from both KONFIDENT and KONFIDENT-S were presented at the European Academy of Allergy and Clinical Immunology Congress 2024. KalVista also filed a New Drug Application (NDA) for sebetralstat with the U.S. FDA in June 2024.
KalVista plans to present additional EU data from the KONFIDENT trial and KONFIDENT-S at the 7th Bradykinin Symposium in Berlin, September 4-6, 2024. They have also started the KONFIDENT-KID trial to assess sebetralstat in children aged 2-11 years.
About the KONFIDENT Phase 3 Trial
The KONFIDENT phase 3 trial is a randomized, double-blind, 3-way crossover study that tested sebetralstat (300 mg and 600 mg) against a placebo in treating HAE. The trial involved 136 patients from 66 sites in 20 countries, making it the largest HAE trial to date. Participants were treated for up to three attacks over the study period.
About the KONFIDENT-S Trial
KONFIDENT-S is an open-label extension trial examining the long-term safety and efficacy of sebetralstat in treating HAE attacks in adults and children aged 12 and older. The trial plans to transition participants to an oral disintegrating tablet (ODT) formulation by Q4 2024, supporting a planned 2026 supplemental NDA (sNDA) filing.
About the KONFIDENT-KID Trial
KONFIDENT-KID is an open-label trial enrolling around 24 children aged 2 to 11 years in seven countries. It will evaluate the safety, pharmacokinetics, and efficacy of a pediatric ODT formulation of sebetralstat. If approved, this would be the first oral on-demand therapy for this age group and the second FDA-approved on-demand therapy for this population.
About Sebetralstat
Sebetralstat is a novel oral plasma kallikrein inhibitor developed by KalVista for on-demand HAE treatment. It has received Fast Track and Orphan Drug Designations from the U.S. FDA and Orphan Drug Designation and an approved Pediatric Investigational Plan from the EMA.
About Hereditary Angioedema
HAE is a rare genetic disorder characterized by deficiencies or dysfunctions in the C1 esterase inhibitor protein, leading to uncontrolled kallikrein-kinin system activation and debilitating swelling attacks. Current on-demand treatments require intravenous or subcutaneous administration.
About KalVista Pharmaceuticals, Inc.
KalVista Pharmaceuticals is dedicated to developing oral medications for conditions with significant unmet needs. The company announced positive phase 3 results for sebetralstat in February 2024 and has submitted both an NDA to the FDA and an MAA to the EMA. KalVista plans to seek approvals in the UK, Japan, and other countries later in 2024.
