KalVista bags FDA approval for delayed oral HAE drug

KalVista Pharma has finally received FDA approval for its oral kallikrein inhibitor sebetralstat, becoming the first treatment in the US that can provide oral, on-demand treatment of hereditary angioedema (HAE) attacks.

The drug has been approved under the Ekterly brand name for use in patients aged 12 and over with HAE, which affects about 1 in 10,000 to 1 in 50,000 people worldwide and leads to unpredictable bouts of debilitating and painful swelling in various parts of the body.

The FDA had been due to deliver a verdict on sebetralstat by 17th June, but the review was delayed, due to what the company suggested was disruption at the agency caused by sweeping job cuts.

There have been unconfirmed reports that FDA Commissioner Marty Makary had sought a complete response letter (CRL) for the application as a punishment for blaming the shake-up at the regulator for the delay, but was prevented from doing so on concerns it would make the agency look capricious.

With that speculation in the past, Anglo-US KalVista can now plan for the launch of what it says will be the first new, on-demand treatment for HAE attacks in a decade, with chief executive Ben Palleiko calling the approval "a defining moment" for people living with the disease. "Ekterly enables people to treat attacks the moment symptoms begin, wherever they are," he said.

There is already an oral plasma kallikrein inhibitor on the market – BioCryst Pharma's Orladeyo (berotralstat). However, that is designed for daily dosing to prevent attacks, while KalVista's drug would be taken when a patient feels an attack coming on. If the swelling in an attack affects areas like the throat or airways, it can have life-threatening consequences.

Even with the use of long-term prophylaxis as a preventative therapy, most people living with HAE continue to have unpredictable attacks and require ready access to on-demand medication, according to KalVista.

Until now, drugs designed to treat acute episodes had to be delivered by subcutaneous injection or infusion, in some cases by a healthcare professional, which can delay treatment. Moreover, these are typically not able to prevent attacks entirely, and sometimes multiple doses are needed to get symptoms under control.

KalVista said it will launch Ekterly immediately and will price it in the same ballpark as other on-demand therapies. Further details will be available after an investor presentation later today.

Other on-demand HAE drugs include Takeda's bradykinin B2 receptor antagonist Firazyr (icatibant) and plasma kallikrein inhibitor Kalbitor (ecallantide), and Pharming's Ruconest and CSL Behring's Berinert, both recombinant C1 esterase inhibitors.

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