Phase 3 trial of sebetralstat meets targeted number of treated attacks
KalVista to seek therapy's US approval in first half of 2024
The trial can wrap up now that three attacks per patient were treated. Topline data is expected in early 2024.
If it’s positive, KalVista Pharmaceuticals, the therapy’s developer, will seek sebetralstat’s U.S. approval in the first half of the year. The company expects to file for approval in the European Union and Japan later in 2024.
“We are excited to have reached the number of on-treatment attacks required for completion of KONFIDENT,” Andrew Crockett, CEO of KalVista, said in a company press release. “We have now initiated study closeout activities which enables topline data readout in early 2024, maintaining the timing of our planned [new drug application] submission in the first half of 2024.”
Swelling attacks in HAE are driven by the overproduction of bradykinin, a molecule that promotes blood vessel widening and permeability, causing fluid to leak and pool into surrounding tissues. The face, lips, tongue, neck, or genitals are most often affected, but swelling can also occur in the throat or intestines.
Sebetralstat is designed to block plasma kallikrein, an enzyme that’s overly active in HAE and controls bradykinin production. Given as an oral film-coated tablet, it’s intended to be taken when an attack begins to prevent it from worsening.
Testing on-demand sebetralstat
Launched early last year, the Phase 3 KONFIDENT trial (NCT05259917), whose design was based on feedback from patients and data from the Phase 2 trial, evaluated the safety and efficacy of the therapy for the same indication.
A total of 136 participants, ages 12 and older, were enrolled at 66 sites across 20 countries. Three attacks were to be treated on demand — one each with 300 mg sebetralstat, 600 mg sebetralstat, and a placebo — in a random order. All the attacks were eligible for treatment, regardless of their location.
According to KalVista, KONFIDENT has achieved this milestone and study completion activities are underway.
The trial’s primary goal was the time to the beginning of symptom relief after the medication was taken, as assessed by the Patient Global Impression of Change (PGI-C), a tool favored by patients.
“We are grateful and highly encouraged by the overwhelming interest in this trial from people living with HAE,” Crockett said. “If approved, we look forward to introducing a novel therapeutic that offers the potential to transform the treatment of this disease.”
KONFIDENT participants who complete the trial can enter KONFIDENT-S (NCT05505916), a two-year open-label extension study designed to evaluate sebetralstat’s long-term safety. The study, which is enrolling up to 150 HAE patients, ages 12 and older, is intended to support the therapy’s planned approval application and is slated to conclude in early 2026.
KalVista is also developing a new formulation of sebetralstat that would quickly dissolve in the mouth instead of being swallowed. Called orally disintegrating tablets (ODT), this administration method may be more convenient for some patients.
A Phase 1 trial showed the ODT formulation had similar pharmacological properties to the film-coated tablets. The U.S. Food and Drug Administration has indicated it doesn’t need additional efficacy data to support the ODT’s development.
KalVista is also testing an oral small molecule called KV998086 as a preventative HAE treatment in preclinical studies.