An innovative orally disintegrating tablet version of sebetralstat, marketed as Ekterly, has demonstrated promising outcomes for treating hereditary angioedema (HAE) in young children, mirroring the effectiveness observed with the standard tablet formulation in adults, according to findings from a phase III clinical study.
The trial’s primary measure focused on plasma concentrations of this oral plasma kallikrein inhibitor achieved 30 minutes after dosing. These levels proved comparable to those seen in adults after taking a 300-mg tablet, with geometric means of 1,364 ng/mL versus 1,810 ng/mL, as presented by Adil Adatia, MD, from the University of Alberta in Edmonton, during the American College of Allergy, Asthma & Immunology annual meeting.
Impressive Interim Efficacy Results
Preliminary data on efficacy revealed that symptom relief commenced within 12 hours for 78.9% of the treated attacks. Remarkably, only 3.1% of these episodes necessitated the use of traditional medications within that same timeframe.
‘Providing children with a fast-acting oral treatment option would represent a significant advancement,’ Adatia emphasized in an interview with MedPage Today.
Historically, hereditary angioedema was thought to primarily manifest symptoms after puberty onset. However, current understanding indicates that approximately 40% of patients experience their initial attack before reaching 5 years old. This prevalence may have been overlooked previously due to many such episodes remaining untreated. A key factor contributing to this is the lack of approved oral therapies; instead, only injectable options are labeled for on-demand management of HAE attacks. In the United States, for children aged 2 to 11 years, the sole approved treatment is intravenous plasma-derived C1 inhibitor.
Adatia shared a poignant example of an adult patient skilled at self-administering infusions but facing challenges with her 5-year-old daughter’s recurrent swelling episodes. The child often cries in distress from the pain, and attempts to insert an IV lead to even greater upset as caregivers struggle to access a small vein. Consequently, prompt intervention at home proves difficult, frequently resulting in emergency department visits for treatment.
Advantages of Dissolvable Tablets for Pediatric Use
‘Medications in dissolvable form are invariably simpler to manage,’ noted Sandra Gawchik, DO, from Asthma and Allergy Associates in Glen Mills, Pennsylvania. ‘Administering a dissolvable tablet to a child with allergies or similar conditions is far more straightforward since swallowing isn’t required. It avoids the mess and variability of liquid formulations while delivering a consistent standard dose.’
Nevertheless, Gawchik stressed that adults must always supervise and administer medications to children under 12 years of age.
The multicenter phase III KONFIDENT-KID study enrolled 36 children between 2 and 11 years old, all confirmed to have HAE due to C1INH deficiency and having suffered at least one attack in the preceding 12 months. Participants received open-label treatment for their attacks using sebetralstat orally disintegrating tablets, dosed according to body weight: 75 mg for the three patients weighing from 9.5 kg up to under 20 kg, 150 mg for the 27 patients in the 20 kg to 45 kg range, and 300 mg for the six children exceeding 45 kg.
Caregivers or the children themselves, assisted by caregivers, could administer the tablets to replicate potential real-world scenarios upon approval. This formulation quickly breaks down upon contact with moisture, allowing placement directly on the tongue followed by a sip of juice, or dissolution in a small amount of liquid, such as a teaspoon of juice, for easier administration, Adatia explained.
Trial Design and Treatment Duration
On-demand treatment persisted for up to 1 year, until the child reached 12 years of age, or until the study concluded. On average, participants managed 0.8 attacks per month with sebetralstat, and 32% of these were still classified as mild when treatment began.
Key secondary outcomes encompassed the time to onset of symptom relief, determined by a Caregiver Global Impression of Change score of at least ‘a little better’ across two consecutive assessments within 12 hours; the time to severity reduction, indicated by a drop in the Caregiver Global Impression of Severity score from baseline over two sequential points within 12 hours; and the time to full resolution of the attack, marked by a severity rating of ‘none’ within 24 hours.
Due to limited attacks in the lowest (one attack) and highest (one attack) dose cohorts, separate evaluations of these endpoints were not feasible. However, in the substantial group receiving 150 mg—where 55 attacks occurred—symptoms began improving at 1.5 hours, severity diminished by 4 hours, and complete resolution was achieved by 12 hours.
Safety Profile and Patient Experience
No children experienced difficulties swallowing the orally disintegrating tablets, and feedback from patients indicated no issues with the taste, according to Adatia during the late-breaking abstract session.
The safety profile was characterized as ‘excellent,’ featuring no treatment-emergent adverse events, whether serious or mild.
