FDA Approval
On July 7, 2025, the U.S. Food and Drug Administration (FDA) approved Ekterly for commercial use in the treatment of acute HAE attacks. This approval was granted based on robust clinical data from Phase III trials, confirming its safety and efficacy. Before Ekterly, all other approved on-demand HAE treatments were injectables, requiring subcutaneous or intravenous administration. Ekterly’s oral format significantly enhances ease of use, portability, and patient adherence.
Mechanism of Action
Ekterly is a selective, reversible inhibitor of plasma kallikrein. Kallikrein is an enzyme involved in the production of bradykinin—a key mediator that causes swelling during an HAE attack. By inhibiting kallikrein, Ekterly effectively blocks the cascade that leads to edema, providing relief from symptoms like abdominal pain, facial swelling, or life-threatening throat swelling (laryngeal edema).
Clinical Trial Data
Ekterly’s approval was based on results from the KONFIDENT Phase III trial, which included 136 patients with HAE. Participants received either a 300 mg dose, a 600 mg dose, or a placebo during separate HAE attacks in a three-way crossover design.
Median time to onset of symptom relief was approximately 1.6 hours for the 300 mg dose and 1.8 hours for the 600 mg dose, compared to nearly 7 hours for the placebo.
Nearly half of the patients taking the 600 mg dose achieved complete symptom resolution within 24 hours, significantly outperforming placebo.
The KONFIDENT-S extension study also showed rapid relief when patients took Ekterly within 10 minutes of symptom onset, with consistent results across over 1,700 attacks.
These trials confirmed that Ekterly is both fast-acting and well-tolerated, even in cases of severe laryngeal or abdominal attacks.
Dosing and Administration
Ekterly is available in 300 mg film-coated tablets. The recommended dose for treating an acute HAE attack is two tablets (600 mg) taken at the first sign of symptoms. If the symptoms persist or return after three hours, a second 600 mg dose may be taken. However, the total daily dose should not exceed 1,200 mg.
For patients taking moderate CYP3A4 inhibitors, the dose may need to be reduced to a single 300 mg tablet. Use of Ekterly is not recommended in patients taking strong CYP3A4 inducers or inhibitors, or in those with severe liver impairment.
Safety and Side Effects
Ekterly demonstrated a favorable safety profile in clinical trials. The most commonly reported side effect was headache. Serious adverse events were rare, and no fatalities or life-threatening events related to the medication were reported.
There are no listed contraindications, but as with any new medication, patients should consult their healthcare provider before use, especially if they are pregnant, breastfeeding, or taking other medications that affect liver enzymes.
