Efficacy of lanadelumab in patients switching from long-term prophylaxis with C1-inhibitor (C1-INH): results from the phase 3 HELP Study

The HELP Study evaluated the efficacy and safety of lanadelumab for long-term prophylaxis (LTP) in hereditary angioedema (HAE). Patients previously on LTP may represent a more severe disease subgroup. Patients aged ≥18 years previously on LTP underwent a 2-week washout prior to the requirement of ≥1 attack in a 4-week run-in period. Patients were randomized and stratified by baseline attack rate into 1 of 4 parallel 26-week treatment arms in a 3:2:2:2 ratio (placebo or lanadelumab [150mg q4wks, 300mg q4wks, 300mg q2wks]). In this exploratory analysis, the Poisson regression model was used to compare the mean HAE attack rate in the lanadelumab groups to placebo by prior LTP use. Historical, run-in, and on-study attack rates for all treatment regimens were analyzed. 125 patients were randomized and treated; 60 (48%) previously used C1-INH-only LTP, 10 (8%) used other treatments and combinations, and 55 (44%) did not use LTP. In C1-INH-only LTP patients, the attack rate was significantly reduced for all lanadelumab regimens versus placebo (P<0.001); the reduction was similar in magnitude to those who did not receive prior LTP. C1-INH-only LTP users reported mean monthly attack rates (3 months prior to the study) of 4.0, 3.0, 2.7 and 2.6; during run-in 4.6, 3.3, 3.7 and 4.6; and during the treatment period 2.9, 0.5, 0.7 and 0.5, for the placebo and lanadelumab 150mg q4wks, 300mg q4wks, and 300mg q2wks groups, respectively. All lanadelumab dosing regimens significantly reduced attack rates versus placebo, regardless of whether patients had received prior C1-INH LTP.