LANADELUMAB SAFETY AND IMMUNOGENICITY: RESULTS FROM THE PHASE 3 HELP STUDY

Abstract

Introduction Lanadelumab, a fully human monoclonal antibody targeting plasma kallikrein, effectively prevented attacks in patients with hereditary angioedema (HAE) in the phase 3 HELP Study (NCT02586805). Methods In HELP, patients ≥12 years with type I/II HAE and ≥1 attack during a 4-week run-in received SC lanadelumab 300 mg q2wks, 300 mg q4wks, 150 mg q4wks, or placebo over 26 weeks. The safety and immunogenicity of repeated doses of lanadelumab were assessed. Results The safety population consisted of 125 patients who received ≥1 dose of study medication; 84 received lanadelumab and 41 received placebo. 78 [92.8%] and 35 [85.4%] patients in lanadelumab and placebo arms completed the study. Treatment emergent AEs (TEAEs) were reported by 76 (90.5%) patients receiving lanadelumab and 31 (75.6%) patients receiving placebo. No serious treatment-related AEs or deaths were reported. One (1.2%) lanadelumab-treated subject had two related hypersensitivity events, one mild and one moderate in severity. Immunogenicity results included ten (11.9%) lanadelumab-treated subjects and 2 (4.9%) placebo-treated subjects with ≥1 treatment-emergent anti-drug antibody (ADA)-positive sample, all at low titers. Two (2.4%) subjects positive for ADA in the 150 mg q4wks arm had low titer neutralizing antibodies. The development of ADA did not impact pharmacokinetics, pharmacodynamics, or clinical response. No safety signals in terms of clinical laboratory tests, vital signs, physical examinations, or ECGs were identified. Conclusions Lanadelumab was generally well tolerated, with few cases of hypersensitivity and low immunogenicity. Together with its efficacy in preventing HAE attacks, lanadelumab may offer patients a novel and well tolerated therapeutic option for HAE prophylaxis.