The phase 3 KONFIDENT trial testing oral sevetralstat as an on-demand treatment for hereditary angioedema (HAE) met its targeted number of swelling attacks during treatment.
The trial will end after three attacks per patient have been treated. Top line data is expected to be released in early 2024.
If it’s positive, calvista pharmaceuticalThe therapy’s developer, sevetralstat, plans to seek approval in the U.S. in the first half of this year. The company plans to apply for approval in the European Union and Japan in the second half of 2024.
“We are excited to have reached the number of attacks in treatment required to complete KONFIDENT,” said Andrew Crockett, CEO of KalVista. corporate press release. “We have now begun study termination activities that will enable topline data readout in early 2024, maintaining the planned timing. [new drug application] It is scheduled to be submitted in the first half of 2024. ”
Swelling attacks in HAE are caused by overproduction of bradykinin, a molecule that promotes blood vessel dilation and permeability, causing fluid to leak and pool in surrounding tissue. The face, lips, tongue, neck, or genitals are most often affected, but swelling can also occur in the throat and intestines.
Sevetralstat is designed to block plasma kallikrein, an enzyme that is overactive in HAE and controls bradykinin production. It is given as an oral film-coated tablet and is meant to be taken when an attack begins to prevent it from getting worse.
Testing sebetralstat on demand
previous Phase 2 study (NCT04208412)on-demand sevetralstat rapidly relieved abdominal and peripheral attacks in 68 adults with HAE who had regular swelling attacks.
Released early last year, Phase 3 KONFIDENT study (NCT05259917)was designed based on patient feedback and data from a phase 2 trial to evaluate the safety and efficacy of the treatment for the same indication.
A total of 136 participants aged 12 years and older were enrolled at 66 sites in 20 countries. The three attacks were to be treated on demand, with each attack receiving 300 mg of sevetralstat, 600 mg of sevetralstat, and placebo in random order. All attacks were eligible for treatment, regardless of where they occurred.
According to KalVista, KONFIDENT has achieved this milestone and study completion activities are underway.
The primary goal of the trial was the time from taking the drug until symptoms began to reduce, as assessed by the Patient Global Impression of Change (PGI-C), a patient-preferred tool.
“We are grateful and very encouraged by the tremendous interest in this trial from people living with HAE,” said Crockett. “We look forward to introducing new treatments that, if approved, have the potential to transform the treatment of this disease.”
KONFIDENT participants who have completed the trial can participate Confident-S (NCT05505916), a 2-year open-label extension study designed to evaluate the long-term safety of sevetralstat. The study will enroll up to 150 HAE patients aged 12 and older and is expected to conclude in early 2026, with the aim of supporting the proposed treatment’s application for approval.
KalVista is also developing a new formulation of sevetralstat that dissolves immediately in the mouth rather than being swallowed. This method of administration, called orally disintegrating tablets (ODT), may be more convenient for some patients.
Phase 1 studies showed that the ODT formulation had pharmacological properties similar to film-coated tablets. The US Food and Drug Administration has indicated that no additional efficacy data are needed to support the development of ODT.
KalVista is also testing an oral small molecule called KV998086 as a preventive HAE treatment in preclinical studies.