Ekterly tablets replacing injections for many in HAE attacks: New data
Oral drug preferred over other options for early on-demand treatment
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For sudden attacks of hereditary angioedema (HAE), many patients prefer — and remain satisfied with — using Ekterly (sebetralstat) oral tablets from Kalvista Therapeutics over other on-demand treatment options, because they are taken by mouth and allow swelling to be treated earlier, with sustained benefits.
That’s according to new data from two clinical trials, which showed that the strongest predictor of faster relief from swelling attacks was early treatment. In both the Phase 3 study KONFIDENT (NCT05259917) and an earlier Phase 2 trial (NCT04208412), taking Ekterly within 30 minutes of symptom onset could help most patients (88.5%) feel better within 12 hours, the data showed.
The results “reinforce the importance of treating HAE attacks early, which is consistently associated with improved outcomes,” Ben Palleiko, CEO of Kalvista, said in a company press release detailing data presented at this year’s American Academy of Allergy, Asthma & Immunology (AAAAI) meeting, held recently in Philadelphia.
“These findings support our belief that Ekterly has the potential to transform how HAE is managed and deliver sustained real-world benefit for people living with HAE,” Palleiko said.
Jonathan A. Bernstein, MD, a professor at the University of Cincinnati College of Medicine in Ohio, shared the data at the AAAAI meeting in a poster titled “Response Drivers in Sebetralstat Placebo-controlled Clinical Trials.”
“Time to treatment is the most robust driver of clinical success in HAE,” Bernstein said. “What is particularly striking is that early intervention proved more predictive of success than the location or severity of the attack.”
For Berstein, Ekterly “doesn’t just offer convenience, it provides a clinical advantage by allowing patients to treat early and consistently to achieve better outcomes.”
Angioedema occurs when fluid collects under the skin or mucous membranes, causing repeated swelling that can occur anywhere in the body. In HAE, genetic mutations cause the body to produce too much bradykinin. Excess bradykinin widens blood vessels and causes fluid to leak into surrounding tissues, increasing the likelihood of swelling attacks.
Ekterly, taken early, shown to prevent worsening of swelling attacks
Ekterly, approved in the U.S. last year, is designed to block kallikrein, an enzyme that is overactive in HAE and controls the amount of bradykinin produced. Given as an oral film-coated tablet, it is intended to be taken as soon as symptoms become evident to prevent worsening of swelling. It is indicated for use in adults and children, ages 12 and older, with HAE.
The therapy’s U.S. approval was based on data from KONFIDENT, which showed that a single dose of Ekterly was sufficient to ease or fully resolve most attacks of swelling in both adolescents and adults. In fact, patients generally experienced relief after a median of two hours.
We [were] observing sustained effectiveness and high patient satisfaction with repeated use of [Ekterly], along with meaningful changes in treatment behavior, including treating the majority of attacks, early intervention, and preference for an oral option.
Participants who completed the clinical study could then enter an ongoing open-label extension called KONFIDENT-S (NCT05505916), in which all patients knew the treatment being given.
“In the KONFIDENT-S open-label extension, we [were] observing sustained effectiveness and high patient satisfaction with repeated use of [Ekterly],” Palleiko said.
Researchers also noted “meaningful changes in treatment behavior, including treating the majority of attacks, early intervention, and preference for an oral option,” Palleiko added.
Across 2,077 attacks reported as of Sept. 2024 in the KONFIDENT-S study, nearly all (98.1%) were treated, according to data shared in another poster at the AAAI meeting. That poster, titled “On-demand Treatment Patterns of Hereditary Angioedema (HAE) Attacks with Sebetralstat in the KONFIDENT-S Study,” was presented by Marc A. Riedl, MD, a professor and clinical director of the U.S. Hereditary Angioedema Association Center at the University of California San Diego.
The data indicated that most patients were treated with Ekterly (82.1%), while fewer were treated with on-demand injectables (16%).
According to Riedl, patients preferred Ekterly, using it for most attacks regardless of severity or location. For the first five attacks, the proportion of patients using injectables dropped from 21% to 13%, while the use of Ekterly increased from 76% to 85%.
With Ekterly, “barriers to treatment of attacks are reduced, including challenges that may exist with injectable medications, potentially facilitating treatment of more attacks,” Riedl said.
The scientist added: “These trends suggest that [Ekterly] may offer an on-demand treatment option that could empower patients to treat disabling HAE symptoms more frequently, and potentially more efficiently, over time.”
Over 80% of patients satisfied or better with oral treatment
Earlier in February, Riedl had presented another poster at the Western Society of Allergy, Asthma & Immunology (WSAAI) scientific session, held in Wailea, Hawaii. That poster was titled “Patterns Associated with Repeated Treatment with Sebetralstat for Multiple HAE Attacks in the KONFIDENT-S Open-Label Study” and showed patients remain satisfied with Ekterly over time.
As of July 2025, patients had used Ekterly to treat 2,464 attacks. Across the first 30 attacks for each patient, slightly fewer than 20% required a second dose, and this need decreased over time.
The data showed that injectables were used in 5.1% of attacks within 12 hours.
On a seven-point scale from extremely dissatisfied to extremely satisfied, 83.1% of attacks treated with Ekterly were rated as satisfied or better, per the poster.
“What is also encouraging is that as patients gained treatment experience, we observed a decreasing trend in the need for both second doses and conventional injectable on-demand therapies. This change in treatment patterns occurred with high levels of patient satisfaction, which was durable over the large number of attacks treated,” Riedl said.
Overall, according to Kalvista, the “presentations highlight patient preference for [Ekterly], early treatment as the strongest driver of response, and sustained effectiveness with [the therapy’s] use in clinical trials.”
