Consistent Lanadelumab Treatment Effect In Patients With Hereditary Angioedema (HAE) Regardless Of Baseline Attack Frequency In The Phase 3 HELP Study

RATIONALE:

Lanadelumab, a fully human monoclonal antibody targeting plasma kallikrein, effectively prevented attacks in patients with HAE in the HELP Study, a phase 3, randomized, double-blind, placebo-controlled study in patients ≥12 years old with symptomatic HAE type I/II (NCT02586805). In an exploratory analysis, efficacy by baseline attack frequency was assessed.

METHODS:

Patients with ≥1 attack/month were randomized to placebo, lanadelumab 150mg q4wks, 300mg q4wks, or 300mg q2wks. The effect of lanadelumab on mean change in monthly attack rates relative to placebo was determined using a Poisson regression model for patients stratified by baseline period attack rates of 1 to <2, 2 to <3, or ³3 attacks/month compared. P-values were unadjusted.

RESULTS:

Of 125 patients, 38 had baseline attack rates of 1 to <2 attacks/month. Compared to placebo (n=12), patients had a 51.0% (150mg q4wks; n=10; P=0.055), 80.4% (300mg q4wks; n=9; P=0.003), and 92.8% (300mg q2wks; n=7; P=0.009) reduction in mean attack rate. Twenty-two patients had baseline attack rates of 2 to <3 attacks. Compared to placebo (n=8), patients had a 90.6% (150mg q4wks; n=3; P=0.001), 77.0% (300mg q4wks; n=5; P<0.001), and 88.2% (300mg q2wks; n=6; P<0.001) reduction in mean attack rate. Similarly, 65 patients with baseline attack rates of ³3 attacks, had a 78.8% (150mg q4wks; n=15; P<0.001), 70.8% (300mg q4wks; n=15; P<0.001), and 85.9% (300mg q2wks; n=14; P<0.001) reduction in mean attack rates relative to placebo (n=21).

CONCLUSIONS:

All three lanadelumab dosing regimens consistently achieved marked reductions in monthly attack rates relative to placebo in patients with HAE, irrespective of baseline attack rate.