FDA to consider sebetralstat as on-demand treatment for HAE
Decision expected by June 2025, Kalvista says
The U.S. Food and Drug Administration (FDA) has agreed to review Kalvista Pharmaceuticals’ application seeking the approval of sebetralstat as an on-demand treatment for swelling attacks in people 12 and older with hereditary angioedema.
Regulators expect to make their decision on the new drug application (NDA) the company submitted in June by June 17, 2025. If approved, sebetralstat would become the first oral, on-demand treatment available to HAE patients in the U.S.
The therapy is also under review in the European Union and Kalvista has indicated plans to make similar requests in other countries, including the U.K. and Japan, by year’s end.
“We are thrilled with the FDA’s acceptance of our NDA for sebetralstat as it moves us one step closer to bringing a potentially transformative therapy to the HAE community,” Ben Palleiko, CEO of Kalvista, said in a company press release. “Given that it could be the first, oral on-demand treatment for HAE, we continue to receive strong support and hear a sense of urgency among healthcare providers, advocates, patients and their families for sebetralstat,” he added.
HAE patients experience sudden swelling attacks affecting the deeper layers of the skin. In some cases, swelling attacks can also affect the airways and become life-threatening.
‘Tremendous burden’
“People living with HAE and their families carry a tremendous burden every day as they don’t know when the next attack may occur or if the attack could cause life-threatening consequences,” Palleiko said.
There are three types of HAE with different underlying genetic causes, but they’re all ultimately characterized by an overproduction of bradykinin, a molecule that regulates blood pressure and inflammation. An excess of bradykinin causes fluid to build up in the deep layers of the skin, leading to swelling.
Sebetralstat is an on-demand therapy designed to block the activity of kallikrein, an enzyme involved in bradykinin production. This is expected to lower bradykinin levels, controlling swelling during an attack.
There are other approved on-demand treatments for HAE attacks, but they’re all given by injection.
Regulatory applications seeking sebetralstat’s approval were based on data from the Phase 3 KONFIDENT clinical trial (NCT05259917) and the ongoing KONFIDENT-S extension study (NCT05505916), which involved HAE patients ages 12 and older.
Results from these studies generally showed that a single dose of sebetralstat could kick-start symptom relief for most patients, with the majority starting to experience relief within two hours of taking sebetralstat — significantly faster than those on a placebo.
The treatment has also been well tolerated, with a safety profile similar to a placebo.
“The compelling data included in our NDA package show that sebetralstat has the potential to significantly alter the way people treat and manage their disease,” Palleiko said.
Treated patients in KONFIDENT and KONFIDENT-S received sebetralstat as film-coated tablets, but Kalvista has since been working on developing an oral disintegrating tablet (ODT) formulation that can dissolve right on the tongue.
The company plans to transition patients remaining in KONFIDENT-S to this new formulation later this year. Data from the study could support a planned 2026 application to the FDA seeking the approval of that formulation.
This ODT formulation is also being used in the ongoing KONFIDENT-KID trial (NCT06467084), launched earlier this year to evaluate sebetralstat as an on-demand treatment for children with HAE, ages 2-11. That study is still seeking children with HAE type 1 or 2 who have had at least one swelling attack in the last year for participation at sites in the U.S.
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