KalVista files first oral on-demand HAE drug with FDA

KalVista Pharma has filed its first marketing application to the US FDA, seeking approval for its oral plasma kallikrein inhibitor sebetralstat as an oral treatment for hereditary angioedema (HAE) attacks.

The filing comes a few months after the Anglo-US biotech reported results from the phase 3 KONFIDENT trial that suggested it could become the first “on-demand” therapy for HAE, a rare condition that causes painful and debilitating attacks characterised by tissue swelling in various parts of the body.

If the swelling affects areas like the throat or airways it can have life-threatening consequences, raising the risk of asphyxiation. HAE is estimated to affect about 1 in 10,000 to 1 in 50,000 people worldwide.

There is already an oral plasma kallikrein inhibitor on the market – BioCryst Pharma’s Orladeyo (berotralstat) – but that is designed for daily dosing to prevent attacks, while KalVista’s drug would be taken when a patient feels an attack coming on.

Meanwhile, other drugs designed to treat acute episodes have to be delivered by subcutaneous injection or infusion – in some cases by a healthcare professional. These are typically not able to prevent attacks entirely, and sometimes multiple doses are needed to get symptoms under control.

That category includes Takeda’s bradykinin B2 receptor antagonist Firazyr (icatibant) and plasma kallikrein inhibitor Kalbitor (ecallantide), Pharming’s recombinant C1 esterase inhibitor Ruconest, and CSL Behring’s recombinant C1 esterase inhibitor Berinert.

In KONFIDENT, sebetralstat met the primary endpoint of achieving symptom relief faster than placebo, with a median time to resolution within two hours versus almost seven hours for the control group. The time to take effect is in the same ballpark as the injectable therapies, with the convenience of just popping a pill.

KalVista’s chief executive, Ben Palleiko, said the filing for use in patients aged 12 and over with HAE represents “a pivotal moment not only for our company, but for the entire HAE community, as we seek to bring an important therapeutic advancement through the first-ever, oral on-demand treatment for HAE.”

The FDA has a 60-day filing review period to determine whether the new drug application (NDA) is complete and accepted for review. Meanwhile, KalVista said it intends to file for approval of sebetralstat with other regulators throughout the remainder of the year.

The company is also working on an oral disintegrating tablet (ODT) formulation of the drug, which could be useful for patients who have attacks affecting the mouth or throat that could make swallowing difficult.

Analysts at Jefferies have previously said that if approved, sebetralstat could make sales of around $500 million a year in the US and Europe.