Increased Response to Higher Dose Lanadelumab in Hereditary Angioedema Patients: Exploratory Findings From the HELP and HELP OLE Studies

The plasma kallikrein inhibitor lanadelumab effectively prevented hereditary angioedema (HAE) attacks compared with placebo in the HELP Study (NCT02586805); 96.4% of lanadelumab-treated patients achieved ≥50% attack rate reduction versus run-in period. We report exploratory findings for HELP Study “nonresponder” patients who had <50% reduction and continued lanadelumab treatment in the HELP Open-Label Extension (OLE; NCT02741596). In the HELP Study, patients ≥12 years old with HAE type I/II and ≥1 attack/month during run-in were randomized to lanadelumab 150mg q4wks, 300mg q4wks, 300mg q2wks, or placebo. Patients continuing to the OLE received a single lanadelumab 300mg dose until first attack, then 300mg q2wks. Individual patient level data are described. Of 84 lanadelumab-treated patients in the HELP Study, 3 were identified as nonresponders; all had received lanadelumab 150mg q4wks, and continued in the OLE with 300mg q2wks. Monthly attack rates (attacks/4 weeks) for patient 1 during the HELP Study run-in (baseline) and treatment period, OLE treatment period, and OLE steady-state period were 1.93, 1.53 (21% reduction), 0.75, and 0.74, respectively. Attack rates for patient 2 were 1.00, 0.92 (8% reduction), 0.63, and 0.82, and for patient 3 were 1.00, 1.82 (82% increase), 0.92, and 0.19. Moderate/severe attack rates were reduced for all 3 patients when receiving 300mg q2wks. Patient 2 experienced 3 laryngeal attacks on 150mg q4wks but none on 300mg q2wks. Patients who did not respond to lanadelumab 150mg q4wks in the HELP Study experienced improvements with 300mg q2wks in the HELP OLE Study.