학술논문
Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks
Document Type
article
Author
Riedl, Marc A; Maurer, Marcus; Bernstein, Jonathan A; Banerji, Aleena; Longhurst, Hilary J; Li, H Henry; Lu, Peng; Hao, James; Juethner, Salomé; Lumry, William R; Hébert, J; Ritchie, B; Sussman, G; Yang, WH; Ettingshausen, C Escuriola; Magerl, M; Martinez‐Saguer, I; Maurer, M; Staubach, P; Zimmer, S; Cicardi, M; Perego, F; Wu, MA; Zanichelli, A; Al‐Ghazawi, A; Shennak, M; Zaragoza‐Urdaz, RH; Ghurye, R; Longhurst, HJ; Zinser, E; Anderson, J; Banerji, A; Baptist, AP; Bernstein, JA; Boggs, PB; Busse, PJ; Christiansen, S; Craig, T; Davis‐Lorton, M; Gierer, S; Gower, RG; Harris, D; Hong, DI; Jacobs, J; Johnston, DT; Levitch, ES; Li, HH; Lockey, RF; Lugar, P; Lumry, WR; Manning, ME; McNeil, DL; Melamed, I; Mostofi, T; Nickel, T; Otto, WR; Petrov, AA; Poarch, K; Radojicic, C; Rehman, SM; Riedl, MA; Schwartz, LB; Shapiro, R; Sher, E; Smith, AM; Smith, TD; Soteres, D; Tachdjian, R; Wedner, HJ; Weinstein, ME; Zafra, H; Zuraw, BL
Source
Allergy. 75(11)
Subject
Language
Abstract
BackgroundLanadelumab demonstrated efficacy in preventing hereditary angioedema (HAE) attacks in the phase 3 HELP Study.ObjectiveTo assess time to onset of effect and long-term efficacy of lanadelumab, based on exploratory findings from the HELP Study.MethodsEligible patients with HAE type I/II received lanadelumab 150 mg every 4 weeks (q4wks), 300 mg q4wks, 300 mg q2wks, or placebo. Ad hoc analyses evaluated day 0-69 findings using a Poisson regression model accounting for overdispersion. Least-squares mean monthly HAE attack rate for lanadelumab was compared with placebo. Intrapatient comparisons for days 0-69 versus steady state (days 70-182) used a paired t test for continuous endpoints or Kappa statistics for categorical endpoints.ResultsOne hundred twenty-five patients were randomized and treated. During days 0-69, mean monthly attack rate was significantly lower with lanadelumab (0.41-0.76) vs placebo (2.04), including attacks requiring acute treatment (0.33-0.61 vs 1.66) and moderate/severe attacks (0.31-0.48 vs 1.33, all P ≤ .001). More patients receiving lanadelumab vs placebo were attack free (37.9%-48.1% vs 7.3%) and responders (85.7%-100% vs 26.8%). During steady state, the efficacy of lanadelumab vs placebo was similar or improved vs days 0-69. Intrapatient differences were significant with lanadelumab 300 mg q4wks for select outcomes. Lanadelumab efficacy was durable-HAE attack rate was consistently lower vs placebo, from the first 2 weeks of treatment through study end. Treatment emergent adverse events were comparable during days 0-69 and 70-182.ConclusionProtection with lanadelumab started from the first dose and continued throughout the entire study period.