D2.329 - Impact of Berotralstat on Quality of Life among Patients with Hereditary Angioedema: Pooled Analysis of the APeX-2 and APeX-J Trials

APeX-2 and APeX-J demonstrated that berotralstat, the only approved targeted oral long-term prophylaxis for hereditary angioedema (HAE), significantly reduces attack rates and is well tolerated. Improvements in quality of life (QoL) were observed, but neither study was powered to detect a difference in QoL outcomes. This study evaluated the impact of berotralstat on QoL using pooled data from the APeX-2 and APeX-J clinical trials.

Data from APeX-2 and APeX-J were pooled for patients receiving berotralstat 150 mg or placebo. QoL was assessed using the Angioedema QoL (AE-QoL) questionnaire, analyzing total and domain scores. Changes from baseline through Week 24 were compared using mixed models for repeated measures (MMRM) to estimate least squares mean differences (LSMDs), with 95% confidence intervals (CI) and p-values. Proportions of patients achieving meaningful improvement were analyzed based on minimal clinically important difference and distribution-based criteria. For patients treated with berotralstat, long-term changes and meaningful improvement through Week 96 were also assessed.

A total of 47 berotralstat and 45 placebo patients were included. At Week 24, berotralstat demonstrated significantly greater improvement in AE-QoL total score (LSMD [95% CI]: -7.4 [-14.3, -0.6], p=0.034), function (-10.9 [-19.6, -2.3], p=0.013), and fears/shame (-8.7 [-17.2, -0.2], p=0.046) domains compared to placebo. Among berotralstat-treated patients, improvements observed at Week 24 were sustained through Week 96, with a trend of improvement over time (average changes from baseline for total score ranging from -15.7 to -25.2). Analyses of meaningful improvement across all measures showed consistent trends, with the proportion of patients achieving meaningful change increasing over time.

Berotralstat provided sustained long-term benefits by significantly improving QoL compared to placebo at Week 24, with these improvements maintained through Week 96. These results suggest that berotralstat both reduces HAE attack frequency and enhances overall patient QoL.