KalVista Pharmaceuticals has announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for sebetralstat, a novel, investigational oral plasma kallikrein inhibitor, for the on-demand treatment of hereditary angioedema (HAE) attacks in adults and pediatric patients aged 12 years and older. This submission marks a significant step toward providing the first oral on-demand treatment option for HAE, a rare genetic disease characterized by painful and debilitating swelling attacks.
The NDA is based on data from the Phase 3 KONFIDENT trial and its extension study, KONFIDENT-S. The KONFIDENT trial, a randomized, double-blind, 3-way crossover study, involved 136 HAE patients across 20 countries. Results showed that both 300 mg and 600 mg formulations of sebetralstat achieved significantly faster symptom relief compared to placebo (p<0.0001 for 300 mg, p=0.0013 for 600 mg). Specifically, the median time to the beginning of symptom relief was 1.61 hours with sebetralstat 300 mg (CI 1.28, 2.27), 1.79 hours with sebetralstat 600 mg (CI 1.33, 2.27), and 6.72 hours with placebo (CI 2.33, >12).
Safety and Tolerability
Sebetralstat demonstrated a favorable safety profile in clinical trials, with tolerability comparable to placebo. No treatment-related serious adverse events (SAEs) were observed, reinforcing the drug's potential as a safe and effective on-demand treatment for HAE.
Addressing Unmet Needs in HAE
Hereditary angioedema is a rare genetic condition affecting an estimated 1 in 50,000 people. It results from a deficiency or dysfunction in the C1 esterase inhibitor (C1INH) protein, leading to uncontrolled activation of the kallikrein-kinin system. Patients experience unpredictable and often severe swelling attacks that can affect various body parts, including the face, throat, abdomen, and limbs. Current on-demand treatments typically require intravenous or subcutaneous administration, posing challenges for some patients, particularly children.
Ben Palleiko, Chief Executive Officer of KalVista, stated, "This NDA submission represents a pivotal moment not only for our company but for the entire HAE community as we seek to bring an important therapeutic advancement through the first-ever, oral on-demand treatment for HAE." He further emphasized the potential of sebetralstat to "transform the way people living with HAE treat their disease."
Future Plans
KalVista anticipates receiving notification from the FDA regarding the NDA's acceptance for review in September. The company also plans to submit additional marketing authorization applications to other global health authorities throughout 2024. Furthermore, KalVista intends to initiate a pediatric trial (KONFIDENT-KID) in Q3 2024 to potentially extend sebetralstat's coverage to patients aged 2-11 years.
An oral disintegrating tablet (ODT) formulation of sebetralstat is also under development, with plans to transition ongoing participants in the KONFIDENT-S trial to this formulation in Q4 2024. If approved, the ODT formulation would offer an alternative, convenient option for oral on-demand treatment.
