KalVista will seek global approvals of sebetralstat for HAE this year
Goal is rapid launch of on-demand treatment if approved in US, Europe, Japan
KalVista Pharmaceuticals plans to submit an application to the U.S. Food and Drug Administration (FDA) in June seeking approval of its oral therapy sebetralstat for the on-demand treatment of hereditary angioedema (HAE), the company announced this week while unveiling its strategic plan for fiscal year 2025.
Similar applications will be submitted, by year’s end, to regulatory agencies in the European Union, the U.K., and Japan, KalVista said in a company press release. The company’s 2025 fiscal year began May 1.
The overall goal, should sebetralstat earn regulatory clearance with each application, is for the rapid launch of the therapy in each of these countries in 2025 and early 2026, per the company. KalVista is looking for commercial partners to help expedite the launches in certain international markets.
These plans follow positive data, released earlier this year, from the Phase 3 KONFIDENT trial (NCT05259917), which showed that the therapy works to ease swelling attacks in adults and adolescents with HAE.
“2024 has been an exciting and busy year for KalVista, as we achieved key milestones with our positive phase 3 KONFIDENT data,” said Ben Palleiko, KalVista’s CEO.
Now, says Palleiko, “we will focus our resources on activities that support the launch, enabling sebetralstat to become the leading on-demand therapy for all people living with HAE.”
Sebetralstat formulation in development would dissolve directly in the mouth
Meanwhile, the company is moving forward with ongoing and planned clinical studies to test an orally disintegrating tablet (ODT) formulation of sebetralstat in HAE patients.
While the original version of sebetralstat is a film-coated tablet that’s swallowed, the ODT version dissolves directly in the mouth. It was designed to make for easier administration for patients with difficulty in swallowing. Such problems may occur during a swelling attack, particularly ones that involve the face, neck, or throat.
The ongoing KONFIDENT-S trial (NCT05505916) is evaluating the long-term safety and effectiveness of sebetralstat in adults and adolescents with HAE over up to two years. It is recruiting up to 150 participants, who may roll over from the earlier KONFIDENT study.
In KONFIDENT-S, participants were originally intended to receive on-demand treatment with sebetralstat (600 mg), given as two film-coated tablets, to manage HAE swelling attacks. Now, the company plans to switch over the KONFIDENT-S participants to the ODT formulation by year’s end. The hope is that trial data would support an eventual regulatory approval of that formulation.
Plans also are in place to launch, in the coming months, the KONFIDENT-KID trial, which will test the ODT formulation in pediatric HAE patients. Should it be eventually approved for children, sebetralstat would be the first oral therapy and the second on-demand treatment approved for that patient population.
For the coming fiscal year, we have set a high bar as we finalize multiple regulatory filings for sebetralstat and plan for rapid commercialization upon approval, [if granted].
Formerly known as KVD900, sebetralstat is an oral small molecule designed to inhibit kallikrein, an enzyme whose overactivity leads to the excessive production of the bradykinin molecule that causes HAE swelling attacks.
When used as an on-demand treatment during a swelling attack, the therapy aims to reduce bradykinin production, thereby easing swelling severity and helping to resolve the attack.
KONFIDENT enrolled 136 HAE patients, ages 12 and older, each of whom received on-demand treatment for three swelling attacks. That included one each treated with 300 mg or 600 mg of sebetralstat, and one with a placebo, in a random order.
Top-line data showed that both doses of sebetralstat led to rapid symptom relief and symptom resolution compared with the placebo. A single dose of the investigational treatment was sufficient to at least kickstart symptom relief or resolution in the majority of treated attacks.
Sebetralstat has earned regulatory designations intended to speed its clinical development in the U.S. and Europe. That includes promising innovative medicine designation in the U.K., fast track and orphan drug status in the U.S., and orphan drug designation in the EU.
“For the coming fiscal year, we have set a high bar as we finalize multiple regulatory filings for sebetralstat and plan for rapid commercialization upon approval,” if granted, Palleiko said.
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