Key Takeaways
FDA approves first oral hereditary angioedema (HAE) therapy: Ekterly (sebetralstat) becomes the first and only FDA-approved oral on-demand treatment for HAE attacks in patients 12 and older.
Phase III trial shows rapid symptom relief: KONFIDENT trial data show Ekterly significantly reduces time to symptom relief and complete attack resolution compared to placebo.
Convenient alternative to injections: Ekterly offers a needle-free option that empowers patients to treat attacks earlier with a more convenitent dosing option, aligning with clinical guidelines.
The FDA has approved KalVista Pharmaceuticals’ Ekterly (sebetralstat) as the first and only oral on-demand treatment for hereditary angioedema (HAE) attacks in patients aged 12 years and older. According to the company, approval was based on results from the Phase III KONFIDENT trial (NCT05259917), which was the largest clinical study ever conducted in HAE. Results from the trial showed faster symptom relief and attack resolution among patients administered Ekterly compared to placebo, along with strong efficacy and a favorable safety profile.1
How does Ekterly Change the Treatment Landscape for HAE?
“The FDA approval of Ekterly is a defining moment for people living with HAE,” said Ben Palleiko, CEO, KalVista, in a press release. “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.”
Phase III KONFIDENT Trial Design
- The randomized, double-blind, placebo-controlled, three-way crossover KONFIDENT trial evaluated the efficacy and safety of 300 mg or 600 mg of Ekterly in 136 patients.
- Patients were randomly assigned to take up to two doses of Ekterly or placebo for an angioedema attack.
- The primary endpoint was time to beginning of symptom relief, defined as a rating of “a little better” or more on the Patient Global Impression of Change (PGI-C) scale at two or more consecutive time points within 12 hours.
- Key secondary endpoints included time to reduction in attack severity (PGI-S scale) within 12 hours and complete attack resolution (PGI-S rating of “none”) within 24 hours.2,3
Trial Results and Clinical Impact
- Results showed that the 300 mg and 600 mg doses of Ekterly significantly reduced the time to symptom relief compared to placebo, with median times of 1.61 and 1.79 hours compared to 6.72 hours.
- Time to reduction in attack severity was also faster: 9.27 hours for 300 mg and 7.75 hours for 600 mg, compared to over 12 hours with placebo.
- Within 24 hours, 42.5% of attacks had resolved with the 300 mg dose and 49.5% with the 600 mg dose, compared to 27.4% with placebo.
- Ekterly was reported to be well tolerated, with no serious adverse events reported.3
“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, CEO, US Hereditary Angioedema Association, in the press release.
What’s Next for KalVista and HAE Patients?
According to KalVista, the findings were further reinforced by the ongoing KONFIDENT-S extension trial, in which patients treated attacks within a median of 10 minutes and experienced symptom relief in a median of 1.3 hours. Ekterly is expected to launch immediately, with physicians now authorized to begin prescribing.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,” KONFIDENT trial investigator Marc A. Riedl, MD, professor of medicine, clinical director, US Hereditary Angioedema Association Center at the University of California, San Diego, said in the press release. “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.”
References
KalVista Pharmaceuticals Announces FDA Approval of EKTERLY® (sebetralstat), First and Only Oral On-demand Treatment for Hereditary Angioedema. BusinessWire. 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
A Phase III, Crossover Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE). Clinicaltrials.gov. Accessed July 7, 2025. https://clinicaltrials.gov/study/NCT05259917?term=KONFIDENT%20&cond=Hereditary%20Angioedema&rank=3
Oral Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks. The New England Journal of Medicine. May 31, 2024. Accessed July 7, 2025. https://www.nejm.org/doi/abs/10.1056/NEJMoa2314192
