Clinical Trial

. 2025 Aug;42(8):3882-3901.

doi: 10.1007/s12325-025-03226-3. Epub 2025 Jun 12.

Sustained Effectiveness, Tolerability, and Safety of Long-Term Prophylaxis with Lanadelumab in Hereditary Angioedema: The Prospective, Phase 4, Noninterventional EMPOWER Real-World Study

Jonathan A Bernstein^{1

2

3}, Stephen D Betschel⁴, Paula J Busse⁵, Aleena Banerji⁶, H James Wedner⁷, Michael Manning⁸, Rafael H Zaragoza-Urdaz⁹, John Anderson¹⁰, Remi Gagnon¹¹, Alan P Baptist¹², Daniel Soteres¹³, William R Lumry¹⁴, Timothy Craig^{15

16}, Daniel Petroni¹⁷, F Ida Hsu¹⁸, Daniel Nova Estepan¹⁹, Salomé Juethner²⁰, Maureen Watt¹⁹, Natalie Khutoryansky¹⁹, Bruce L Zuraw²¹; EMPOWER Investigators

Collaborators, Affiliations

Collaborators

EMPOWER Investigators:
Alan P Baptist, Paula J Busse, Hugo Chapdelaine, Selina Gierer, M Dawn Goodyear, Douglas Johnston, Jay Kashkin, Paul K Keith, Alexander Kim, H Henry Li, Richard Lockey, Patricia Lugar, Jason Raasch, Raffi Tachdjian, Mark Weinstein

Affiliations

¹ Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML#563, Cincinnati, OH, 45267-0563, USA. bernstja@ucmail.uc.edu.
² Advanced Allergy Services LLC, Cincinnati, OH, USA. bernstja@ucmail.uc.edu.
³ Bernstein Clinical Research Center, Cincinnati, OH, USA. bernstja@ucmail.uc.edu.
⁴ Division of Clinical Immunology and Allergy, Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁵ Division of Allergy and Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Division of Allergy & Immunology, Washington University School of Medicine in St Louis, St Louis, MO, USA.
⁸ Allergy, Asthma & Immunology Associates, Ltd., Scottsdale, AZ, USA.
⁹ University of Puerto Rico School of Medicine and University Pediatric Hospital, San Juan, Puerto Rico.
¹⁰ AllerVie Health, Birmingham, AL, USA.
¹¹ Clinique Spécialisée en Allergie de la Capitale, Quebec, QC, Canada.
¹² Division of Allergy and Immunology, Henry Ford Health, Detroit, MI, USA.
¹³ Asthma & Allergy Associates, P.C., Colorado Springs, CO, USA.
¹⁴ Allergy and Asthma Research Associates, Dallas, TX, USA.
¹⁵ Allergy, Asthma and Immunology, Departments of Medicine, Pediatrics and Biomedical Sciences, ACARE International Hereditary Angioedema Resource Center, Penn State University, Hershey, PA, USA.
¹⁶ Vinmec International Hospital, Times City, Hanoi, Vietnam.
¹⁷ Seattle Allergy and Asthma Research Institute, Seattle, WA, USA.
¹⁸ Section of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
¹⁹ Takeda Development Center Americas, Inc., Lexington, MA, USA.
²⁰ Takeda Pharmaceuticals USA, Inc., Lexington, MA, USA.
²¹ Division of Allergy & Immunology, University of California San Diego, La Jolla, CA, USA.

PMID: 40504359
PMCID: PMC12313730
DOI: 10.1007/s12325-025-03226-3

Clinical Trial

Sustained Effectiveness, Tolerability, and Safety of Long-Term Prophylaxis with Lanadelumab in Hereditary Angioedema: The Prospective, Phase 4, Noninterventional EMPOWER Real-World Study

Jonathan A Bernstein et al. Adv Ther. 2025 Aug.

. 2025 Aug;42(8):3882-3901.

doi: 10.1007/s12325-025-03226-3. Epub 2025 Jun 12.

Authors

Collaborators

EMPOWER Investigators:
Alan P Baptist, Paula J Busse, Hugo Chapdelaine, Selina Gierer, M Dawn Goodyear, Douglas Johnston, Jay Kashkin, Paul K Keith, Alexander Kim, H Henry Li, Richard Lockey, Patricia Lugar, Jason Raasch, Raffi Tachdjian, Mark Weinstein

Affiliations

¹ Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML#563, Cincinnati, OH, 45267-0563, USA. bernstja@ucmail.uc.edu.
² Advanced Allergy Services LLC, Cincinnati, OH, USA. bernstja@ucmail.uc.edu.
³ Bernstein Clinical Research Center, Cincinnati, OH, USA. bernstja@ucmail.uc.edu.
⁴ Division of Clinical Immunology and Allergy, Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁵ Division of Allergy and Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Division of Allergy & Immunology, Washington University School of Medicine in St Louis, St Louis, MO, USA.
⁸ Allergy, Asthma & Immunology Associates, Ltd., Scottsdale, AZ, USA.
⁹ University of Puerto Rico School of Medicine and University Pediatric Hospital, San Juan, Puerto Rico.
¹⁰ AllerVie Health, Birmingham, AL, USA.
¹¹ Clinique Spécialisée en Allergie de la Capitale, Quebec, QC, Canada.
¹² Division of Allergy and Immunology, Henry Ford Health, Detroit, MI, USA.
¹³ Asthma & Allergy Associates, P.C., Colorado Springs, CO, USA.
¹⁴ Allergy and Asthma Research Associates, Dallas, TX, USA.
¹⁵ Allergy, Asthma and Immunology, Departments of Medicine, Pediatrics and Biomedical Sciences, ACARE International Hereditary Angioedema Resource Center, Penn State University, Hershey, PA, USA.
¹⁶ Vinmec International Hospital, Times City, Hanoi, Vietnam.
¹⁷ Seattle Allergy and Asthma Research Institute, Seattle, WA, USA.
¹⁸ Section of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
¹⁹ Takeda Development Center Americas, Inc., Lexington, MA, USA.
²⁰ Takeda Pharmaceuticals USA, Inc., Lexington, MA, USA.
²¹ Division of Allergy & Immunology, University of California San Diego, La Jolla, CA, USA.

PMID: 40504359
PMCID: PMC12313730
DOI: 10.1007/s12325-025-03226-3

Abstract

Introduction: Lanadelumab is approved for long-term prophylaxis of hereditary angioedema (HAE) attacks in patients aged ≥ 2 years in the USA and aged ≥ 12 years in Canada. The EMPOWER Study (NCT03845400) evaluated the real-world effectiveness and safety of lanadelumab in male and female patients with HAE due to C1 inhibitor deficiency type 1 or 2 from the USA and Canada. Here, we report final, up to 36-month, data.

Methods: Patients aged ≥ 12 years were classified as newly treated with lanadelumab or established on lanadelumab (receiving < 4 and ≥ 4 lanadelumab doses at enrollment, respectively). The primary objective was effectiveness of lanadelumab as measured by HAE attack rate before and after lanadelumab initiation. Safety data were collected.

Results: A total of 109 patients received ≥ 1 lanadelumab dose and had ≥ 1 post-baseline safety assessment. Patients were 40.9 (17.4) years of age (mean [standard deviation (SD)]), majority (72/109; 66.1%) female, 37/109 (33.9%) male, and over 90% white. Patients newly treated with and established on lanadelumab received lanadelumab for 737.7 (374.5) (mean [SD]) and 907.1 (469.3) days, respectively, during the study. In patients newly treated with lanadelumab, the mean (95% confidence interval) observed attack rate (attacks/month) decreased by 85% after lanadelumab initiation, from 1.42 (0.34-2.50) pre-lanadelumab to 0.20 (0.02-0.38) post-lanadelumab initiation (cumulative period). Patients established on lanadelumab had an observed attack rate of 0.20 (0.10-0.30) during 36 months' follow-up. Of 154 treatment-emergent adverse events (TEAEs), no injection site reactions were reported and 6 (in 2 patients) were considered related to lanadelumab; no lanadelumab-related TEAEs were serious.

Conclusion: Real-world data from EMPOWER showed marked HAE attack rate reduction up to 36 months after initiating lanadelumab in patients newly treated with lanadelumab and maintenance of low attack rates in patients established on lanadelumab. No new safety signals were identified.

Trial registration: ClinicalTrials.gov, identifier NCT03845400. Graphical abstract available for this article.

Keywords: Effectiveness; Hereditary angioedema; Lanadelumab; Long-term prophylaxis; Real-world data; Safety.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of Interest: Jonathan A. Bernstein has been or is currently a clinical investigator for BioCryst, BioMarin Pharmaceutical, CSL Behring, Ionis, KalVista Pharmaceuticals, Pharming Group, and Takeda; consultant for BioCryst, BioMarin Pharmaceutical, CSL Behring, Ionis, KalVista Pharmaceuticals, Pharming Group, and Takeda; and a member of the Hereditary Angioedema Medical Advisory Board and US Hereditary Angioedema Association. Stephen D. Betschel has been a speaker and/or received advisor fees from Astria Therapeutics, BioCryst, CSL Behring, Ionis, KalVista Pharmaceuticals, Pharvaris, and Takeda; and research funding from CSL Behring and Takeda. Paula J. Busse has received research support and served on advisory boards for ADARx, Astria Therapeutics, BioCryst, CSL Behring, Intellia Therapeutics, KalVista Pharmaceuticals, and Takeda; and is a consultant for CVS Pharmacy. Aleena Banerji has received research support from Astria Therapeutics, Ionis, and Takeda; and been an advisory board member for ADARx Pharmaceuticals, Astria Therapeutics, BioCryst, BioMarin Pharmaceutical, CSL Behring, Intellia Therapeutics, KalVista Pharmaceuticals, Pharvaris, and Takeda. H. James Wedner has received research support from Astria Therapeutics, BioCryst, CSL Behring, Ionis, KalVista Pharmaceuticals, Pharming Group, Pharvaris, and Takeda; been a speaker for BioCryst, BioMarin Pharmaceutical, Blueprint Medicines, CSL Behring, KalVista Pharmaceuticals, Pharming Group, and Takeda; and consulted for ADARx Pharmaceuticals, Astria Therapeutics, BioCryst, CSL Behring, Ionis, KalVista Pharmaceuticals, Pharming Group, and Takeda. Michael Manning has been a researcher/primary investigator and speaker/consultant for BioCryst, BioMarin Pharmaceutical, CSL Behring, Ionis, KalVista Pharmaceuticals, Pharming Group, Pharvaris, and Takeda. Rafael H. Zaragoza-Urdaz has been or is currently a clinical investigator for KalVista Pharmaceuticals, Pharvaris, and Takeda; has received honoraria from/been a member of a speaker’s bureau for BioCryst, CSL Behring, Pharming Group, and Takeda; been an advisory board member for BioCryst, Pharming Group, Regeneron, and Takeda; and received research support from AstraZeneca, GlaxoSmithKline, KalVista Pharmaceuticals, and Takeda. John Anderson has received personal fees for steering committee, advisory board, speaker bureau, and/or clinical research activity from BioCryst, BioMarin Pharmaceutical, CSL Behring, Cycle Pharmaceuticals, KabiCare, KalVista Pharmaceuticals, Pharming Group, Pharvaris, and Shire/Takeda. Remi Gagnon has served as a researcher for ALK-Abelló, AstraZeneca, DBV Technologies, GlaxoSmithKline, Moderna, Novartis, Regeneron, Sanofi, and Takeda; been an advisory board member for ALK-Abelló, Bausch & Lomb, Regeneron, Sanofi Genzyme, and Takeda; and received fees for speaker bureaus from Bausch & Lomb and Novartis. Alan P. Baptist reports research support from BioCryst, Ionis, and Takeda. Daniel Soteres is an advisor for CSL Behring, Cycle Pharmaceuticals, KalVista Pharmaceuticals, and Shire/Takeda; consultant for BioCryst, KalVista Pharmaceuticals, and Pharming Group; conducted research for BioCryst, BioMarin Pharmaceutical, Ionis, KalVista Pharmaceuticals, Pharvaris, and Shire/Takeda; and a speaker for BioCryst, CSL Behring, Pharming Group, and Shire/Takeda. William R. Lumry is a member of advisory boards for Astria Therapeutics, BioCryst, BioMarin Pharmaceutical, CSL Behring, Intellia Therapeutics, KalVista Pharmaceuticals, Pharvaris, and Takeda; received research grants from BioCryst, BioMarin Pharmaceutical, CSL Behring, Ionis, KalVista Pharmaceuticals, and Takeda; consulting fees from Astria Therapeutics, BioCryst, CSL Behring, Fresenius Kabi, Pharming Group, and Takeda; payments for lectures from CSL Behring, Pharming Group, and Takeda; and is an advisory board member of the US Hereditary Angioedema Association. Timothy Craig has served as a speaker and researcher for Astria Therapeutics, BioMarin Pharmaceutical, Ionis, CSL Behring, Intellia Therapeutics, KalVista Pharmaceuticals, and Takeda; researcher for Pharvaris; speaker for Grifols; consultant for Astria Therapeutics, BioCryst, BioMarin Pharmaceutical, CSL Behring, Intellia Therapeutics, Ionis, and Takeda; Director for ACARE International Hereditary Angioedema Center; and member of the Medical Advisory Board for the HAE-A. Timothy Craig is an Editorial Board member of Advances in Therapy. Timothy Craig was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Daniel Petroni reports advisory boards for Takeda and has been a research/primary investigator for BioCryst and Takeda; he is now an employee of BioCryst. F. Ida Hsu received research support from Takeda; served on advisory boards for BioCryst, CSL Behring, KalVista Pharmaceuticals, and Takeda; was a speaker for Amgen, Pharming, and Shire/Takeda; and is a consultant for Intellia Therapeutics. Daniel Nova Estepan and Maureen Watt are employees of Takeda Development Center Americas, Inc. and hold stock and/or share options in Takeda Pharmaceutical Company Limited. Salomé Juethner is an employee of Takeda Pharmaceuticals USA, Inc., and holds stock and/or share options in Takeda Pharmaceutical Company Limited. Natalie Khutoryansky is an employee of Cytel, contracted by Takeda Development Center Americas, Inc. Bruce L. Zuraw has received consulting fees from Adverum Biotechnologies, BioCryst, CSL Behring, and Takeda. Ethical Approval: EMPOWER was conducted in accordance with the International Council for Harmonisation Good Clinical Practice Guidelines, ethical principles that have their origins in the Declaration of Helsinki, and other local ethical and legal requirements. The study was reviewed and approved in all study sites by a central review board (Western-Copernicus Group [WCG] Institutional Review Board) or institutions’ local ethics committees (Table S1 in the Supplementary Material). All patients or their legally authorized representatives provided informed consent to participate in the study.

Figures

**Fig. 1**
EMPOWER Study periods. ^aPatient recall or physician assessment of the patient’s medical history for ≤ 6 months before enrollment. ^bDefined only for patients newly treated with lanadelumab. ^cDefined only for patients established on lanadelumab

**Fig. 3**
Mean observed HAE attack rates before and after lanadelumab initiation (full analysis set). Median observed HAE attack rates (attacks/month) in patients newly treated with lanadelumab at enrollment were 0.39 pre-lanadelumab and 0.10 in the cumulative period; and 0.06 attacks/month during the overall study period in patients established on lanadelumab at enrollment. CI confidence interval, *HAE* hereditary angioedema, *IRR* incidence rate ratio

**Fig. 4**
Mean adjusted^a model-estimated HAE attack rates before and after lanadelumab initiation in patients newly treated with lanadelumab at enrollment (full analysis set; as treated). ^aModel adjusted for sex and age at lanadelumab initiation. CI confidence interval, *HAE* hereditary angioedema, *IRR* incidence rate ratio

See this image and copyright information in PMC

References

1. Christiansen SC, Wilmot J, Castaldo AJ, Zuraw BL. The US Hereditary Angioedema Association Scientific Registry: hereditary angioedema demographics, disease severity, and comorbidities. Ann Allergy Asthma Immunol. 2023;131:766–74.e8. - PubMed
1. Bernstein JA. Severity of hereditary angioedema, prevalence, and diagnostic considerations. Am J Manag Care. 2018;24:S292–8. - PubMed
1. Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema—the 2021 revision and update. Allergy. 2022;77:1961–90. - PubMed
1. Busse PJ, Christiansen SC, Riedl MA, et al. US HAEA Medical Advisory Board 2020 guidelines for the management of hereditary angioedema. J Allergy Clin Immunol Pract. 2021;9:132–50.e3. - PubMed
1. Bygum A, Busse P, Caballero T, Maurer M. Disease severity, activity, impact, and control and how to assess them in patients with hereditary angioedema. Front Med (Lausanne). 2017;4:212. - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

Associated data

Actions
- Search in PubMed
- Search in ClinicalTrials.gov

LinkOut - more resources

Full Text Sources
- PubMed Central
- Springer
Medical
- ClinicalTrials.gov

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Sustained Effectiveness, Tolerability, and Safety of Long-Term Prophylaxis with Lanadelumab in Hereditary Angioedema: The Prospective, Phase 4, Noninterventional EMPOWER Real-World Study

Collaborators

Affiliations

Sustained Effectiveness, Tolerability, and Safety of Long-Term Prophylaxis with Lanadelumab in Hereditary Angioedema: The Prospective, Phase 4, Noninterventional EMPOWER Real-World Study

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical