@article{998212a5de97431892b0bef1c5a31aa9,
title = "Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks",
abstract = "Background: Lanadelumab demonstrated efficacy in preventing hereditary angioedema (HAE) attacks in the phase 3 HELP Study. Objective: To assess time to onset of effect and long-term efficacy of lanadelumab, based on exploratory findings from the HELP Study. Methods: Eligible 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. Results: One 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. Conclusion: Protection with lanadelumab started from the first dose and continued throughout the entire study period.",
keywords = "durable efficacy, hereditary angioedema, long-term prophylaxis, onset of action",
author = "{for the HELP Investigators} and Riedl, {Marc A.} and Marcus Maurer and Bernstein, {Jonathan A.} and Aleena Banerji and Longhurst, {Hilary J.} and Li, {H. Henry} and Peng Lu and James Hao and Salom{\'e} Juethner and Lumry, {William R.} and J. H{\'e}bert and B. Ritchie and G. Sussman and Yang, {W. H.} and {Escuriola Ettingshausen}, C. and M. Magerl and I. Martinez-Saguer and M. Maurer and P. Staubach and S. Zimmer and M. Cicardi and F. Perego and Wu, {M. A.} and A. Zanichelli and A. Al-Ghazawi and M. Shennak and Zaragoza-Urdaz, {R. H.} and R. Ghurye and Longhurst, {H. J.} and E. Zinser and J. Anderson and A. Banerji and Baptist, {A. P.} and Bernstein, {J. A.} and Boggs, {P. B.} and Busse, {P. J.} and S. Christiansen and T. Craig and M. Davis-Lorton and S. Gierer and Gower, {R. G.} and D. Harris and Hong, {D. I.} and J. Jacobs and Johnston, {D. T.} and Levitch, {E. S.} and Li, {H. H.} and Lockey, {R. F.} and P. Lugar and Lumry, {W. R.}",
note = "Funding Information: We thank all patients, investigators, and their study staff. The HELP Study was sponsored by Shire Human Genetic Therapies, Inc, a Takeda company, Lexington, MA, USA. Under direction of the authors, Sophia Shumyatsky, PharmD, CMPP, employee of Excel Medical Affairs, provided writing assistance for this manuscript. Editorial assistance in formatting, proofreading, copy editing, and fact‐checking also was provided by Excel Medical Affairs. Shire Human Genetic Therapies, Inc, a Takeda company, provided funding to Excel Medical Affairs for support in writing and editing this manuscript. The interpretation of the data was made by the authors independently. Funding Information: MAR has received research grants from BioCryst, CSL Behring, Pharming, and Shire*; consulting fees from Adverum, Attune, BioCryst, CSL Behring, KalVista, Pharming, Pharvaris, and Shire*; and speaker honoraria from CSL Behring, Pharming, and Shire; and is a medical advisory board member of the US Hereditary Angioedema Association. MM has received research grant support and/or speaker/consultancy fees from Adverum, Attune, BioCryst, CSL Behring, KalVista, Pharming, Pharvaris, and Shire.* JAB has been a clinical investigator for BioCryst, CSL Behring, Pharming, and Shire*; a speaker for CSL Behring, Pharming, and Shire*; and a consultant for BioCryst, CSL Behring, Kabi, KalVista, Pharming, and Shire*; and is a medical advisory board member of the US Hereditary Angioedema Association. AB has received institutional research/study support from BioCryst and Shire* and/or honoraria for consulting from BioCryst, CSL Behring, KalVista, Pharming, Pharvaris, and Shire.* HJL has received research grant support and/or speaker/consultancy fees from Adverum, BioCryst, CSL Behring, Octapharma, Pharming, and Shire.* HHL has been a clinical investigator and received grants and/or honoraria from BioCryst, CSL Behring, Pharming, and Shire.* PL was a full‐time employee of Shire* at the time of this analysis and holds stock/stock options in Takeda. Her current affiliation is Pharvaris B.V. JH and SJ are full‐time employees of Shire* and hold stock/stock options in Takeda. WRL has received consultant fees from Adverum, BioCryst, CSL Behring, Pharming, and Shire*; research grants from BioCryst, CSL Behring, Pharming, and Shire*; and payments for lectures from CSL Behring, Pharming, and Shire*; and is a medical advisory board member of the US Hereditary Angioedema Association. ",
year = "2020",
month = nov,
day = "1",
doi = "10.1111/all.14416",
language = "English (US)",
volume = "75",
pages = "2879--2887",
journal = "Allergy: European Journal of Allergy and Clinical Immunology",
issn = "0105-4538",
publisher = "Wiley-Blackwell",
number = "11",
}