Efficacy and safety of lanadelumab for prophylactic treatment in adolescents with hereditary angioedema (HAE)

The efficacy and safety of lanadelumab, a monoclonal antibody targeting plasma kallikrein, in adolescents with HAE with C1-inhibitor deficiency (HAE-C1-INH) were investigated in a phase 3 trial and its open-label extension. In a multicenter, double-blind trial (NCT02586805), patients aged ≥12 years with ≥1 investigator-confirmed attack/4 weeks were randomized to placebo, or 150 mg every 4 weeks (150 mg q4w), 300 mg q4w, or 300 mg q2w lanadelumab. In the open-label extension study (NCT02741596; May 2016-September 2017), rollover patients from the phase 3 study and non-rollover patients received 300 mg q2w. Monthly attack rate (MAR) and other treatment-emergent events (TEAEs) were recorded. In the phase 3 trial, 10/125 patients (8%) were adolescents (aged ≥12 to <18 years). In the placebo, 150 mg q4w, 300 mg q4w, and 300 mg q2w arms, respectively, 4, 1, 3, and 2 patients had a mean (SD) MAR of 1.825 (1.460), 1.000, 0.989 (0.020), and 1.948 (1.341) during the run-in period and 0.917 (0.992), 0.000, 0.304 (0.263), and 0.306 (0.433) during the treatment period. Three patients had 13 non-serious lanadelumab-related TEAEs. In the extension study, 21/212 patients (9.9%) were adolescents. Rollover patients (n=8) and non-rollover patients (n=13), respectively, had a mean (SD) MAR of 1.65 (1.158) and 1.54 (0.971) at baseline and 0.35 (0.635) and 0.07 (0.166) during the treatment period, ie, a mean (SD) percent change of -84.37 (18.94) and -94.89 (10.52). Nine patients had 65 non-serious lanadelumab-related TEAEs. Lanadelumab safely reduced the MAR in adolescents with HAE-C1-INH.