HAE Guidelines Reinforce Early On-Demand Treatment, With Mauro Cancian, MD, PhD

Updated international guidelines for hereditary angioedema (HAE) place renewed emphasis on early, on-demand treatment.1

The guidelines recommend sebetralstat (Ekterly), an oral plasma kallikrein inhibitor approved by the US Food & Drug Administration in July 2025, as a first-line option for the acute treatment of attacks in patients aged ≥ 12 years.2 In an interview with HCPLive, Mauro Cancian, MD, PhD, head of the allergy division at the University of Padua, discussed how data from the phase 3 KONFIDENT study contributed to this guideline change.

“The result has been very interesting, because there has been a reduction in the interval between onset of symptoms and treatment compared with previous, available treatments that were only injectable,” Cancian said.

KONFIDENT, which assessed sebetralstat in adolescents and adults with HAE, showed that the drug is very quick at stopping disease progression and improving symptoms. As of January 31, 2025, investigators found that the median time from attack onset to treatment was 4 minutes, the median time to the beginning of symptom relief was 1.79 hours, to the reduction in severity was 3.53 hours, and to complete attack resolution was 15.09 hours.2 In the open-label extension, treatment delays were shorter, which Cancian attributed in part to the portability and ease of administration of sebetralstat.

“[The] main delay now is less than 10 minutes,” Cancian said. “That's not a delay. [It] is really every treatment because…10 minutes is the time you…recognize that an attack is happening.”

HAE due to C1 esterase inhibitor deficiency is characterized by recurrent, bradykinin-mediated swelling that can involve the extremities, gastrointestinal tract, and airway. Historically, acute treatment options have required intravenous or subcutaneous administration, including plasma-derived or recombinant C1 inhibitor and the bradykinin B2 receptor antagonist icatibant.1 These agents are effective but may introduce practical barriers that delay administration outside clinical settings.

Cancian cautioned that long-term prophylaxis, though increasingly effective, does not eliminate breakthrough attacks. Therefore, reliable on-demand treatment remains essential even for patients receiving preventive therapy.

Limitations remain, including the absence of head-to-head trials comparing oral and injectable agents and the need for additional real-world effectiveness data. Pediatric use is currently limited to patients aged ≥ 12 years.

Overall, the updated guidelines formalize a management strategy centered on early intervention, individualized care, and maintaining quality of life.

“What we are emphasizing with our patients, and obviously as a result of the guideline, is that to make [a] more effective treatment, you have to treat [the attacks] as early as possible,” Cancian said. “That means treating at the onset of the attack because we know that if there is a delay between attack onset and treatment, the drug will be less effective in reducing both the severity and the duration of the attacks.”

References

1. Farkas H, Martinez-Saguer I, Bork K, et al. International Guideline on the Diagnosis and Management of Pediatric Patients With Hereditary Angioedema. Allergy. Published online January 30, 2026. doi:10.1111/all.70207 

2. Johnson V. Sebetralstat FDA-Approved as First Oral, On-Demand for Hereditary Angioedema. HCPLive. Published on July 7, 2025. Accessed on February 23, 2026. https://www.hcplive.com/view/sebetralstat-fda-approved-as-first-oral-on-demand-for-hereditary-angioedema