Sebetralstat FDA-Approved as First Oral, On-Demand for Hereditary Angioedema

The FDA has approved sebetralstat, the first and only oral, on-demand therapy for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. KalVista Pharmaceuticals’ therapy, approved on July 7, will be marketed under the name Ekterly.1

“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,” investigator Marc A. Riedl, MD, Professor of Medicine and Clinical Director, U.S. Hereditary Angioedema Association Center at the University of California, San Diego, said in a statement.1 “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.”

Sebetralstat is a novel plasma kallikrein inhibitor that was evaluated in the phase 3 KONFIDENT (NCT05259917) and KONFIDENT-S open-label extension (NCT05505916) trials. Data from the trials were recently presented at March’s 2025 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress in San Diego, California supporting the approval.2

“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,” Anthony J. Castaldo, chief executive officer of the U.S. Hereditary Angioedema Association, added.1

At the AAAAI/WAO Joint Congress, investigators presented pooled data from attacks treated with sebetralstat 600 mg by adolescents (12-17 years) in KONFIDENT and KONFIDENT-S. Investigators evaluated the time to beginning of symptom relief, time to reduction in attack severity (both within 12 hours), and time to complete resolution within 24 hours.

As of January 31, 2025, investigators found that in 19 adolescents, the median time from attack onset to treatment was 4.0 minutes (IQR, 1.0-52.0). The median time to beginning of symptom relief was 1.79 hours (range, 0.76-7.12), to reduction in severity was 3.53 hours (range, 0.81->12), and to complete attack resolution was 15.09 hours (range, 3.52->24). The investigators reported 12 treatment-emergent adverse events (AE) in 6 adolescents (31.6%); 1 AE of tremor in 1 participant was treatment related. There were no study discontinuations.1

These adolescent findings followed topiline results from KONFIDENT published in 2024 that demonstrated the beginning of symptom relief occurred in a median of 1.3 hours among attacks involving the larynx, the abdomen, and for breakthrough attacks among patients receiving long-term prophylaxis in 136 patients with HAE.3

“The FDA approval of EKTERLY is a defining moment for people living with HAE,” Ben Palleiko, CEO of KalVista, added.1 “EKTERLY enables people to treat attacks the moment symptoms begin, wherever they are. This approval affirms the strength of our science and deep commitment to the HAE community. I am profoundly grateful to the KalVista team for their dedication and perseverance, and to the patients and healthcare providers, as well as the HAEA and HAEi, for making this possible. EKTERLY has the potential to become the foundational treatment for HAE and our focus now is on delivering it to the people who need it.”

REFERENCES

1. KalVista Pharmaceuticals Announces FDA Approval of EKTERLY® (sebetralstat), First and Only Oral On-demand Treatment for Hereditary Angioedema. News release. KalVista Pharmaceuticals. 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. Cohn D, Kessell A, Kinaciyan T, et al. On-demand Treatment Of Hereditary Angioedema Attacks With Sebetralstat In Adolescents: Pooled Analysis From KONFIDENT And KONFIDENT-S. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3. Abstract 552.

3. Riedl MA, Farkas H, Aygören-Pürsün E, et al. Oral Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks. New Eng J Med. 2024;391(1):32–43.