151:
Consistent Lanadelumab Treatment Effect In Patients With Hereditary Angioedema (HAE) Regardless Of Baseline Attack Frequency In The Phase 3 HELP Study
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Marc A. Riedl, MD MS, Raffi Tachdjian, MD MPH, Jennifer Schranz, MD, Christina Nurse, PhD, Jonathan A. Bernstein, MD FAAAAI
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.