D2.357 - Reductions in Hereditary Angioedema Attacks among Patients with C1 Esterase Inhibitor Deficiency who Switched from Another Long-Term Prophylaxis to Berotralstat

Hereditary angioedema (HAE) is a rare genetic condition characterized by recurring swelling attacks that can be life-threatening. This real-world study compared HAE attack rates before and after initiation of berotralstat—the only targeted, once-daily, oral long-term prophylaxis (LTP) —among patients with HAE with C1 esterase inhibitor deficiency (HAE-C1INH; type 1 or 2) who switched from a prior LTP.

This retrospective pre-post study used specialty pharmacy data (December 3, 2020 – September 10, 2025) from Optime Care, Inc., the sole dispenser of berotralstat in the United States. Patients were eligible if they had ≥2 berotralstat dispensings (first dispensing = index), HAE-C1INH based on laboratory measurements (C1INH levels, C1INH function, and C4 levels), ≥90 days of follow-up (spanning from first to last berotralstat dispensing), a self-assessment of attacks during baseline (90 days pre-index), and ≥1 self-assessment of attacks during follow-up. Eligible patients also reported using another LTP prior to berotralstat initiation and discontinuing this medication within the 60 days before or after index (i.e., switched). Monthly HAE attack rates in follow-up (segmented into fixed 90-day intervals) were compared with baseline among patients with follow-up through the end of a given 90-day interval and ≥1 self-assessment of attacks in the 90-day interval. Comparisons used mean differences, 95% confidence intervals (CIs), and p-values from generalized estimating equations linear regression models with robust standard errors.

Among 120 eligible patients with HAE-C1INH who switched from another LTP to berotralstat, mean age was 42.5 years and over half (55.8%) were female. Most patients switched from either lanadelumab (37.5%) or subcutaneous plasma-derived C1INH (26.7%). Mean baseline attack rates were 1.77, 1.54, and 1.82 attacks/month among patients with ≥12, ≥24, and ≥36 months of follow-up, respectively. Monthly attack rate reductions (95% CIs) were -1.16 (-1.78, -0.55) at 12 months, -0.88 (-1.53, -0.23) at 24 months, and -1.22 (-2.13, -0.31) at 36 months of follow-up (all p<0.001) (Figure).

Among patients with HAE-C1INH who switched from another LTP, berotralstat was associated with significant and sustained real-world HAE attack rate reductions.