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

As updated hereditary angioedema (HAE) 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 HCPLive, 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.1,2

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.”

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. 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