Berotralstat and Health-Related Quality of Life in Hereditary Angioedema: Pooled Analysis of the APeX-2 and APeX-J Trials.

BACKGROUND

In the phase 3 APeX-2 and APeX-J trials, improvements in health-related quality of life (HRQoL) were reported for berotralstat, the only oral, once-daily, long-term prophylaxis for hereditary angioedema (HAE). We conducted a post hoc trial analysis to evaluate the impact of berotralstat on HRQoL versus placebo through 24 weeks, and the long-term effects of treatment up to 96 weeks, using pooled APeX-2 and APeX-J patient data.

METHODS

Patients receiving berotralstat 150 mg or placebo using the Angioedema QoL (AE-QoL) questionnaire; total and domain scores were analysed. 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 nominal p-values. After Week 24, in the absence of a placebo comparator, long-term changes from baseline were evaluated using within-subject effect sizes (Cohen's d) through Week 96 in patients receiving berotralstat. Clinical meaningful improvements in AE-QoL total and domain scores were assessed by minimal clinically important difference (6-point reduction in AE-QoL total score) and distributional criterion methods, respectively. The manufacturer of berotralstat (BioCryst Pharmaceuticals) funded this study.

RESULTS

Overall, 47 and 45 patients received berotralstat and placebo, respectively. At Week 24, berotralstat showed significantly greater improvement in AE-QoL total (LSMD: -7.4; 95% CI: -14.3, -0.6; p < 0.05), functioning domain (LSMD: -10.9; 95% CI: -19.6, -2.3; p = 0.013) and fears/shame domain (LSMD: -8.7; 95% CI: -17.2, -0.2; p = 0.046) scores compared with placebo. Among patients receiving berotralstat, consistent sustained improvements were observed across all AE-QoL domains up to Week 96. Analyses of meaningful improvement in total score and domains showed an increase over time in the proportion of patients achieving meaningful change.

CONCLUSION

Berotralstat significantly improved HRQoL versus placebo through 24 weeks and showed long-term beneficial effects through 96 weeks.