Mauro Cancian, MD, PhD, head of the allergy division at the University of Padua.

Mauro Cancian, MD, PhD

Transitioning to Oral On-Demand HAE Therapy, With Mauro Cancian, MD, PhD

guidelines reinforce early, patient-controlled treatment, questions remain about how clinicians should approach transitioning patients from injectable on-demand therapies to oral options. In an interview with 

, Mauro Cancian, MD, PhD, head of the allergy division at the University of Padua, discussed practical considerations following results from the phase 3 KONFIDENT trial of oral sebetralstat.

The updated international guidance emphasizes treating attacks at symptom onset and ensuring all patients have reliable access to effective on-demand therapy.² Historically, acute treatment has relied on injectable agents such as plasma-derived or recombinant C1 inhibitor and the bradykinin B2 receptor antagonist icatibant. These therapies have demonstrated efficacy but may introduce logistical challenges that delay administration, particularly outside clinical settings.

According to Cancian, the primary consideration in transitioning to an oral option is treatment burden, eliminating pain and the need to carry around an injectable therapy. He noted that injectable therapies require preparation, storage, and administration that may complicate travel or daily activities. In contrast, oral tablets may reduce both practical and psychological barriers to early treatment.

“Obviously, patients usually prefer to take a pill because [it] is easier…having appeal reduces the burden of treatment,” Cancian said. “There is no special plan for transition. You [only] ask patients.”

He said that, typically, patients not used to HAE treatments prefer to start with oral, not injectable, drugs. However, for patients used to injectable drugs, he advised clinicians to inform their patients that the oral option is very effective and safe.

He acknowledged that some patients may perceive injectable therapies as inherently more potent, a belief shaped in part by emergency department practices where intravenous medications are common. Cancian emphasized that efficacy and safety data from KONFIDENT support the use of oral sebetralstat for acute treatment.¹ The trial demonstrated significantly shorter time to beginning of symptom relief compared with placebo in adolescents and adults with type I or II HAE.¹

Regarding limitations, Cancian noted that, as with most clinical trials, KONFIDENT enrolled selected patients with well-characterized disease, which may not fully reflect heterogeneous real-world populations. However, he pointed to findings from the open-label extension, which suggested sustained efficacy and shorter delays to treatment initiation as patients became more confident using the medication.

Cancian said he would like to see longer-term real-world data confirming the durability of response across attack types, including laryngeal and gastrointestinal episodes, and continued evaluation for potential rebound phenomena observed with some injectable agents. He also highlighted the importance of pediatric studies in children < 12 years, a population with substantial treatment burden.

“The takeaway is…the opportunity to treat [HAE] attacks by oral tablets, which allow[s] [for treating] early,” he said. “Only early treatment allows patients to be adherent [and]…to normalize their life.”

Farkas H, Martinez-Saguer I, Bork K, et al. International Guideline on the Diagnosis and Management of Pediatric Patients With Hereditary Angioedema. 

Cancian M. HAE Guidelines Reinforce Early On-Demand Treatment, With Mauro Cancian, MD, PhD. HCPLive. Published on February 23, 2026. Accessed on February 24, 2026. 

https://www.hcplive.com/view/hae-guidelines-reinforce-early-demand-treatment-mauro-cancian-md-phd

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Updated HAE guidelines support early self-treatment; Cancian discuss transitioning patients from injectable on-demand therapy to oral sebetralstat after KONFIDENT data.

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

place renewed emphasis on early, on-demand treatment.

The guidelines recommend sebetralstat (Ekterly), an oral plasma kallikrein inhibitor approved by the 

 in July 2025, as a first-line option for the acute treatment of attacks in patients aged ≥ 12 years.

, 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.

 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.

 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.”

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

KONFIDENT investigator Cancian discusses oral sebetralstat’s role in the updated HAE treatment guidelines.

Mauro Cancian, MD, PhD

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