UK innovation passport issued to sebetralstat as treatment for HAE

Designation aims to shorten time to potential approval for therapy

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Sebetralstat, an oral small molecule being developed by KalVista Pharmaceuticals as an on-demand treatment for hereditary angioedema (HAE), has been issued an innovation passport by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA).

An innovation passport is the first step into the U.K.’s Innovative Licensing and Access Pathway, known as ILAP. This pathway is a mechanism that aims to shorten the time it takes for potential approval of a medication, with the goal of getting new treatments into the market more quickly for patients with unmet medical needs.

“As a company which has its roots in the UK, we are pleased to receive the ILAP designation, which will enable us to further accelerate our regulatory submission for sebetralstat,” Andrew Crockett, CEO of KalVista, said in a company press release.

KalVista is planning to submit an application in the coming months in the U.S. to request the therapy’s approval, with similar submissions in the European Union, and in Japan, expected later this year. Those approval requests, similar to any that is made in the U.K., is expected to be based on top-line data from a Phase 3 clinical trial called KONFIDENT (NCT05259917), in which sebetralstat brought swelling under control within two hours.

“We look forward to collaborating with the MHRA and other health regulatory agencies worldwide as we continue to work towards bringing the first oral, on demand treatment to people living with HAE,” Crockett said.

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Sebetralstat shown in KONFIDANT trial to be effective as treatment for HAE

In HAE, genetic mutations result in a faulty or missing C1 inhibitor protein. This, in turn, causes an enzyme called kallikrein to drive the excessive production and release of bradykinin. Excess bradykinin causes blood vessels to leak fluid into nearby tissues, resulting in repeated attacks of swelling.

Sebetralstat, formerly known as KVD900, is a small molecule designed to block kallikrein’s activity in the bloodstream. On-demand treatment with the medication is expected to readily bring swelling under control, reducing the severity and duration of attacks as they happen.

The KONFIDENT trial tested how well sebetralstat worked in 136 adults and adolescents, ages 12 and older, with HAE type 1 or 2. All received on-demand treatment for three attacks of swelling, one each with film-coated tablets containing either 300 or 600 mg of sebetralstat or a placebo, in a random order.

The trial met its main goal of reducing the time to symptom relief versus a placebo, which was defined as patients feeling at least a little better within 12 hours of dosing. The median time to symptom relief was 1.6 hours with the lower dose of sebetralstat and 1.8 hours with the higher one, compared with 6.7 hours with the placebo.

Sebetralstat also was found to be well tolerated, with no serious side effects reported. In KONFIDENT, the proportion of treatment-related side effect was actually lower in patients given sebetralstat than in those treated with the placebo.

The company plans to present its latest clinical data later this month at the upcoming American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting, which will be held in Washington.

Sebetralstat has been granted fast track and orphan drug designations in the U.S. It also has been granted orphan drug designation in Europe, where a pediatric investigational plan has been given the green light.

The newly issued innovation passport is delivered by the U.K.’s MHRA in partnership with the All Wales Therapeutics and Toxicology Centre (AWTTC), the National Institute for Health and Care Excellence (NICE), and the Scottish Medicines Consortium (SMC).