FDA approves sebetralstat as first and only on-demand treatment for HAE | Image Credit: Contemporary Pediatrics

On July 7, 2025, the FDA approved KalVista Pharmaceuticals' novel plasma kallikrein inhibitor sebetralstat (Ekterly) to treat acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older, according to a press release from the company. With the approval, sebetralstat becomes the first and only oral, on-demand treatment for HAE.¹

Prior to approval, all on-demand treatment for HAE approved in the United States required intravenous or subcutaneous administration.

“This is an important moment for patients, giving people living with HAE a treatment option that could provide greater independence and control over managing their condition,” said Marc A. Riedl, MD, in a statement. Riedl is a professor of Medicine and clinical director, US Hereditary Angioedema Association Center at the University of California, San Diego, and an investigator for the KONFIDENT phase 3 trial.

“Until now, on-demand treatment relied on injectable subcutaneous or intravenous administration, often resulting in delayed intervention. Having an oral option empowers patients to treat attacks early, which aligns with treatment guidelines and advances our goal as physicians to reduce the overall burden of disease," added Riedl.

Data that led to sebetralstat approval

Approval was based on results from the phase 3 KONFIDENT trial, which demonstrated statistically significant faster symptom relief, reduction in attack severity, and attack resolution compared to placebo. Additionally, sebetralstat was well tolerated and had a similar safety profile to placebo.

According to trial results published in the New England Journal of Medicine, there were 136 patients assigned to 1 of 6 trial sequences, with 110 treating 264 attacks. The time to the beginning of symptom relief was faster than placebo in both the 300 mg and 600 mg dose (P < 0.001 and P = 0.001 for the two comparisons, respectively), with median times of 1.61 hours (interquartile range, 0.78 to 7.04), 1.79 hours (1.02 to 3.79), and 6.72 hours (1.34 to >12), respectively.²

With median times of 9.27 hours (interquartile range, 1.53 to >12), 7.75 hours (2.19 to >12), and more than 12 hours (6.23 to >12), the time to reduction in the attack severity was faster in the 300 mg and 600 mg doses compared to placebo (P = 0.004 and P = 0.003).

Percentage of attack with complete resolution in a 24-hour period was 42.5% with the 300 mg dose and 49.5% with the 600 mg dose, with placebo offering a 27.4% reduction.

“As the first orally administered on-demand therapy for HAE attacks, EKTERLY provides patients and physicians with an important and welcome advance in HAE treatment options,” said Anthony J. Castaldo, chief executive officer of the US Hereditary Angioedema Association, in a press release.¹

Sebetralstat approved after original target date

The July 7 approval comes several weeks after the original Prescription Drug User Fee Act date of June 17, 2025, because of heavy workload and limited resources at the FDA, which forced the agency to push the decision. The federal agency did not request additional data or studies and has not raised any concern about the safety, efficacy, or approvability of sebetralstat.³

The new drug application for sebetralstat was accepted by the FDA on September 3, 2024.

References:

1. KalVista Pharmaceuticals announces FDA approval of Ekterly (sebetralstat), first and only oral on-demand treatment for hereditary angioedema. KalVista Pharmaceuticals. Press release. July 7, 2025. Accessed July 7, 2025. https://www.businesswire.com/news/home/20250702871458/en/KalVista-Pharmaceuticals-Announces-FDA-Approval-of-EKTERLY-sebetralstat-First-and-Only-Oral-On-demand-Treatment-for-Hereditary-Angioedema

2. Riedl MA, Farkas H, Aygören-Pürsün E, et al. Oral sebetralstat for on-demand treatment of hereditary angioedema attacks. N Engl J Med. 2024;391(1):32–43.

3. Fitch J. FDA will not meet original PDUFA date for sebetralstat to treat HAE. Contemporary Pediatrics. June 16, 2025. Accessed July 7, 2025. https://www.contemporarypediatrics.com/view/fda-will-not-meet-original-pdufa-data-for-sebetralstat-to-treat-hae