Kalvista asks 4 countries to OK sebetralstat as treatment for HAE
Approval sought in UK, Switzerland, Australia, Singapore
Kalvista Pharmaceuticals has submitted applications to regulatory authorities in the U.K., Switzerland, Australia, and Singapore requesting the approval of sebetralstat, an oral, on-demand treatment for hereditary angioedema (HAE) in patients ages 12 and older.
The four applications were submitted through the Access Consortium framework, a coalition of regulatory authorities working together to promote and maximize collaboration across countries and support a timely regulatory review process.
Regulatory authorities in the U.S. and the European Union have agreed to review similar applications requesting sebetralstat’s approval. A decision from the U.S. Food and Drug Administration (FDA) is expected by June 17, 2025.
News of the latest submissions “further underscores our focus and dedication to getting sebetralstat to as many people living with HAE as possible,” Ben Palleiko, Kalvista’s CEO, said in a company press release. “To serve that goal, we are building a global commercial presence to provide the greatest possible access to potentially the first oral on-demand treatment for this debilitating disease,” Palleiko said.
HAE is characterized by an overproduction of bradykinin, a molecule that regulates blood pressure and inflammation by promoting blood vessel widening. An excess of bradykinin causes fluid to build up in the deep layers of the skin or mucous membranes, leading to swelling attacks.
First oral treatment for HAE swelling attacks
Sebetralstat is an oral small molecule that’s designed to inhibit the activity of kallikrein, an enzyme involved in bradykinin production. This is expected to lower bradykinin levels during swelling attacks, reducing the severity and duration of the attacks as they occur.
Although there are several on-demand therapies for HAE, they are all administered by injection. If approved, sebetralstat will be the first oral treatment available to treat swelling attacks.
The regulatory applications are supported by data from the Phase 3 KONFIDENT trial (NCT05259917) and its ongoing, open-label extension study KONFIDENT-S (NCT05505916), testing the treatment in more than 100 HAE patients ages 12 and older.
Patients in the studies had HAE types 1 or 2 and at least two documented swelling attacks in the 90 days before they were randomly assigned to receive either one of two doses of sebetralstat (300 or 600 mg) or a placebo to treat their first attack. Over the course of the study, all patients used both doses of the therapy and the placebo to treat up to three attacks in a random order. For each attack, participants could take the therapy twice if needed.
Top-line data from KONFIDENT showed that both doses of sebetralstat significantly accelerated the start of symptom relief, with most patients experiencing relief within two hours, as opposed to more than six hours with the placebo.
Similar observations were made in the extension study, with sebetralstat enabling patients to start experiencing symptom relief within a median of one hour and 48 minutes.
The company plans to transition any remaining patients receiving sebetralstat in KONFIDENT-S in the form of film-coated tablets to an oral, disintegrating-tablet formulation this year, to support a regulatory submission in 2026 seeking the approval of an additional formulation of the therapy.
That formulation is also being tested in the Phase 3 KONFIDENT-KID trial (NCT06467084), which is designed to evaluate the safety and efficacy of the therapy in children with HAE types 1 or 2, ages 2 to 11, who had at least one attack in the previous year. The trial, which launched earlier this year, is recruiting patients at sites in the U.S., with additional sites expected to open in Europe and Asia.
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