KalVista Submits FDA Application for Sebetralstat as First Oral On-demand Hereditary Angioedema Treatment

KalVista Pharmaceuticals, Inc., a biopharmaceutical company listed on NASDAQ, has announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for their investigational drug, sebetralstat. This novel oral plasma kallikrein inhibitor is designed for the on-demand treatment of hereditary angioedema (HAE) attacks in patients aged 12 and older.

KalVista’s CEO, Ben Palleiko, highlighted the significance of this milestone, emphasizing that the NDA submission marks a critical step forward for both the company and the HAE community. Sebetralstat stands out as the first oral on-demand treatment for HAE, offering a potentially transformative approach to managing this rare disease. The submission reflects extensive collaboration between KalVista, HAE patients, scientific communities, and regulatory bodies.

The NDA is supported by data from comprehensive clinical trials, notably the KONFIDENT phase 3 trial and its extension, KONFIDENT-S. In the phase 3 trial, sebetralstat demonstrated significant efficacy, with 300 mg and 600 mg doses achieving quicker symptom relief compared to placebo. Specifically, the median time to symptom relief was 1.61 hours for the 300 mg dose, 1.79 hours for the 600 mg dose, and 6.72 hours for the placebo. These results underscore the drug's potential to offer rapid relief from HAE attacks.

Sebetralstat has shown a favorable safety profile across all studies, with no serious adverse events linked to the treatment. The FDA now has a 60-day period to review the completeness of the NDA submission. KalVista expects to receive feedback from the FDA by September and plans to seek further marketing authorizations globally throughout 2024.

If approved, sebetralstat will be the pioneering oral therapy for HAE, which could be especially beneficial for younger patients who often face difficulties with injectable treatments. KalVista also intends to initiate the KONFIDENT-KID trial in the third quarter of 2024. This trial will target children aged 2-11, potentially leading to an extended approval for this age group in the future.

KalVista plans to present additional data from their clinical trials at the 2024 Annual Scientific Conference of the American College of Allergy, Asthma, and Immunology (ACAAI) in Boston. The KONFIDENT phase 3 trial was the most extensive HAE clinical trial to date, involving 136 patients from 66 sites across 20 countries. The trial included both type 1 and type 2 HAE patients who had experienced at least two attacks within 90 days prior to the study.

The open-label KONFIDENT-S trial is examining the long-term safety and efficacy of sebetralstat. KalVista aims to transition participants to an oral disintegrating tablet (ODT) formulation by late 2024, paving the way for a potential supplemental NDA in 2026. This ODT formulation could provide an innovative alternative for HAE patients.

Sebetralstat, developed by KalVista, is a pioneering oral plasma kallikrein inhibitor aimed at treating HAE on demand. It has received Fast Track and Orphan Drug Designations from the FDA, as well as Orphan Drug Designation and a Pediatric Investigational Plan approval from the European Medicines Agency.

Hereditary angioedema is a rare genetic disorder characterized by the deficiency or dysfunction of the C1 esterase inhibitor protein, leading to unpredictable and painful swelling attacks. Current treatments require intravenous or subcutaneous administration, underscoring the potential game-changing impact of an effective oral therapy like sebetralstat.

KalVista Pharmaceuticals is dedicated to developing oral treatments for diseases with unmet medical needs. The company's promising results from the KONFIDENT trial position sebetralstat as a potential breakthrough therapy for HAE. KalVista is also preparing for regulatory submissions in the UK, Europe, and Japan later this year.