D2.498 - Berotralstat Decreased HAE Attacks Treated with On-Demand Therapy or Utilizing Professional Care in Pediatric Patients Aged 2 to

Hereditary angioedema (HAE) symptoms can occur early in life, and HAE attacks are often treated with on-demand therapy or medical care. Long-term prophylactic (LTP) treatments for children aged <12 years have historically been limited to parenteral administration, which is especially challenging in pediatric patients and highlights the need for oral LTP options. Berotralstat, an oral small-molecule plasma kallikrein inhibitor approved for HAE LTP in patients aged ≥12 years, was recently approved in the United States for children aged 2 to <12 years. This is an updated analysis of 48-week data from the ongoing APeX-P clinical trial for patients aged <12 years with HAE.

APeX-P (NCT05453968; EU CTN 2024-511257-22-00) is an open-label study evaluating the pharmacokinetics, efficacy, and safety of berotralstat in patients with HAE aged 2 to <12 years and weighing ≥12 kg. Before berotralstat initiation, patients received standard of care (SoC) for 12 weeks, including LTP and/or on-demand therapy. HAE attacks treated with on-demand therapy or utilizing professional care were compared between SoC and berotralstat treatment through 48 weeks. Incidence of adverse events (AEs) was assessed.

Overall, patients (N=29; 48.3% female) had a median (range) age of 8.0 (3–11) years. Median (range) age at HAE symptom onset was 2.0 (0.3–8.0) years, and most (82.8%) had symptom onset before 6 years. A total of 27 (93.1%) patients completed at least 48 weeks of berotralstat treatment. Overall, HAE attacks treated with on-demand treatment decreased from median (range) 0.691 (0–5.03) attacks/month during the 12-week SoC period to 0.169 (0–1.75) attacks/month from Day 1 through Week 48 of berotralstat treatment. The number of HAE attacks where professional care was utilized decreased from 22 in the 12-week SoC period to 9 from Day 1 through Week 48 of treatment. The most common treatment-emergent AEs throughout the treatment period were nasopharyngitis (34.5%), upper respiratory tract infection (27.6%), and vomiting (17.2%). There were no drug-related Grade 3/4 AEs, drug-related serious AEs, deaths, or discontinuations related to AEs.

The updated analysis of the APeX-P trial demonstrates that HAE attacks treated with on-demand therapy or utilizing professional care reduced after berotralstat initiation and remained low through 48 weeks. Berotralstat was safe, generally well tolerated, and is a promising alternative LTP therapy for pediatric patients aged 2 to <12 years.