Ekterly reduces anxiety tied to HAE attacks, new study finds
Treatment led to quicker improvement than placebo in trial
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On-demand treatment with Ekterly (sebetralstat), marketed by Kalvista Pharmaceuticals for hereditary angioedema (HAE), reduced anxiety associated with swelling attacks more quickly and effectively than a placebo in a recent study.
“Moderate-to-extreme anxiety was common,” the researchers wrote, but it eased with treatment, particularly in patients who were most worried about their swelling. The data come from KONFIDENT (NCT05259917), a Phase 3 clinical study that supported Ekterly’s approval in the U.S. last year.
The study, “Impact of Oral Sebetralstat on Anxiety Associated with Hereditary Angioedema Attacks,” was published in Clinical & Experimental Allergy. It was funded by Kalvista Pharmaceuticals.
HAE swelling attacks can be unpredictable and distressing
Angioedema occurs when fluid builds up in tissues, triggering swelling. In HAE, genetic changes lead to excess production of bradykinin, a molecule that widens blood vessels and allows fluid to leak into surrounding tissues. Because attacks are unpredictable and most treatments are given by injection — which can be uncomfortable or inconvenient — many patients feel anxious.
Ekterly is designed to block kallikrein, an enzyme that is overactive in HAE and helps control how much bradykinin is produced. It is available as an oral, film-coated tablet that is taken as soon as symptoms begin to prevent swelling from worsening. It is approved for use in adults and children with HAE ages 12 and older.
In KONFIDENT, a single dose of Ekterly was sufficient to start relieving symptoms in most attacks. In this study, the researchers also examined whether on-demand treatment with Ekterly could ease the anxiety that comes with sudden swelling attacks.
As part of the study, patients took either Ekterly (300 or 600 mg) or a placebo soon after an attack began. Anxiety was measured over 24 hours using the General Anxiety Numeric Rating Scale (GA-NRS), which ranges from zero (no anxiety) to 10 (extreme anxiety). A meaningful improvement was defined as at least a two-point drop on the scale that was sustained across two consecutive measurements.
Many HAE attacks linked to moderate-to-high anxiety levels
Among 261 swelling attacks with available anxiety data, 115 (44%) were linked to moderate-to-extreme anxiety. At the time of treatment, the median GA-NRS score was three. Women reported more severe anxiety than men, as did patients who had been more recently diagnosed and those experiencing more severe attacks.
Patients who took Ekterly had a significantly greater reduction in their GA-NRS score than those who took a placebo. This effect was seen over time, including at 12 and 24 hours after treatment, and was more pronounced with the higher dose. They also experienced faster relief from anxiety, reaching a meaningful improvement in a median of 2.3 hours, compared with more than 12 hours for placebo.
When researchers also considered physical symptoms, they found that patients who experienced earlier symptom relief also reported meaningful improvements in anxiety. Similar patterns were seen in patients whose attacks became less severe within 12 hours or fully resolved within 24 hours. These findings suggest that improvements in physical symptoms are associated with reduced emotional distress.
“Managing anxiety, and tools to address anxiety in HAE remain an area of unmet need,” the researchers wrote. “Addressing anxiety in a comprehensive manner, alongside managing the physical symptoms of HAE, is vital to improving patients’ overall quality of life and empowering them to live more fulfilling lives.”
