Berotralstat: A data review of a novel oral medication for the treatment of hereditary angioedema


  • Jason Ohayon, MD, FRCPC McMaster University;



The treatment of hereditary angioedema (HAE) has progressed significantly over the last decade. HAE is an autosomal dominant condition that is bradykinin mediated and affects approximately 1 in 50,000 people. This condition continues to challenge allergists/immunologists (A/I) in promptly managing the disease to reduce attacks of potentially life-threatening angioedema, while improving quality of life in a population in which disease activity tends to increase with age. Notably, delays in diagnosis may reach up to 8 years from initial presentation. The impact of HAE extends beyond the patient, and can affect their caregivers, owing to the fear of acute attacks, which can lead to absenteeism both at school and in the workplace and ultimately negatively impact quality of life and career productivity.

Author Biography

Jason Ohayon, MD, FRCPC, McMaster University;

Dr. Jason Ohayon completed his pediatric residency at McMaster in 1996 and Allergy Clinical Immunology in 1998. He consults in Allergy/ Immunology, for both Children and Adults for the SW Ontario region. He is on staff at Hamilton Health Sciences and St. Joseph’s Hospital and instructs in the Michael DeGroote School of Medicine. Dr. Ohayon’s current clinical interest is in modification of allergic skin and GI disease and in allergic desensitization. Dr. Ohayon serves as a Peer Assessor for the CPSO is a member of the Canadian, American and European Allergy Societies. He is the Research Director of Hamilton Allergy, and co-founder of iCASE Allergy Associates whose mission is to provide practicing Allergists an educative and supportive medium for collaboration. He maintains a private consulting office in West Hamilton.


Caccia S, Suffritti C, Cicardi M. Pathophysiology of hereditary angioedema. Pediatr Allergy Immunol Pulmonol. 2014;27(4):159-163. doi: 10.1089/ped.2014.0425

Zanichelli A, Magerl M, Longhurst HJ, Aberer W, Caballero T, Bouillet, L, et al. Improvement in diagnostic delays over time in patients with hereditary angioedema: findings from the Icatibant Outcome Survey. Clin Transl Allergy. 2018;12:8:42. doi: 10.1186/s13601-018-0229-4

Lumry Castaldo AJ, Vernon MK, Blaustein MB, Wilson DA, Horn PT. The humanistic burden of hereditary angioedema: impact on health-related quality of life, productivity, and depression. Allergy Asthma Proc. 2010;31(5):407-414. doi:10.2500/aap.2010.31.3394

Bork Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol. 2012;130(3):692-697. doi: 10.1016/j.jaci.2012.05.055

Henao MP, Kraschnewski JL, Kelbel T, Craig TJ. Diagnosis and screening of patients with hereditary angioedema in primary care. Ther Clin Risk Manag. 2016;12:701-711. Doi: 10.2147/TCRM.S86293

Reshef Zanichelli A, Longhurst H, Relan A, Hack CE. Elevated D-dimers in attacks of hereditary angioedema are not associated with increased thrombotic risk. Allergy. 2015;70(5):506-513. doi: 10.1111/all.12587

Bork K, Witzke G. Shortened activated partial thromboplastin time may help in diagnosing hereditary and acquired angioedema. Int Arch Allergy Immunol. 2016;170(2):101-107. doi: 10.1159/000447695

Longhurst HJ, Bork K. Hereditary angioedema: an update on causes, manifestations and treatment. Br J Hosp Med (Lond). 2019;80(7) 391-398. doi: 10.12968/hmed.2019.80.7.391

Longhurst HJ, Zanichelli A, Caballero T, Boillet L, Aberer W, Mauer M, et al. Comparing acquired angioedema with hereditary angioedema (types I/II): findings from the Icatibant Outcome Survey. Clin Exp Immunol. 2017;188(1):148-153. doi: 10.1111/cei.12910

Bork K, Wulff K, Hardt J, Witzke G, Staubach P. Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy. J Allergy Clin Immunol. 2009;124(1):129-134. doi: 10.1016/j.jaci.2009.03.038

Maurer M, Magerl M, Betschel S, Aberer W, Ansotegui IJ, Aygören-Pürsün E, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022;77(7):1961-1990. doi: 10.1111/all.15214

Zanichelli A, Vacchini R, Badini M, Penna V, Cicardi M. Standard care impact on angioedema because of hereditary C1 inhibitor de­ficiency: a 21-month prospective study in a cohort of 103 patients. Allergy. 2011;66(2):192-196. doi: 10.1111/j.1398-9995.2010.02433.x

Valerieva A, Staevska M, Jesenak M, Hrubiskova K, Sobotkova M, Zachova R, et al. Recombinant human C1 esterase inhibitor as short-term prophylaxis in patients with hered­itary angioedema. J Allergy Clin lmmunol Pract. 2020;8(2):799-802. doi: 10.1016/j.jaip.2019.08.011

Maurer M, Aygören-Pürsün E , Banerji A, Bernstein JA, Balle Boysen H, Busse PJ, et al. Consensus on treat­ment goals in hereditary angioedema: a global Delphi initiative. J Allergy Clin lmmunol. 2021;148(6):1526-1532. doi: 10.1016/j.jaci.2021.05.016

Craig T, Zuraw B, Longhurst H, Cicardi M, Bork K, Gratten C, et al. Long-term outcomes with subcutaneous C1-inhibitor replacement therapy for prevention of hereditary angioedema attacks. J Allergy Clin lmmunol Pract. 2019;7(6):1793-1802 e2. doi: 10.1016/j.jaip.2019.01.054

Hahn J, Trainotti S, Wigand MC, Schuler PJ, Hoffmann TK, Greve J. Prospective analysis in patients with HAE under prophy­laxis with lanadelumab: a real-life experience. J Drugs Dermatol. 2020;19(10):978-983. doi:10.36849/JDD.2020.5269

Zuraw B, Lumry WR, Johnston DT, Aygören-Pürsün E, Banerji jA, Bernstein JA, et al. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: a randomized, double-blind, placebo-controlled phase 3 trial. J Allergy Clin Immunol. 2021;148(1) 164-172.e9. doi: 10.1016/j.jaci.2020.10.015

Bernstein JA, Li HH, Craig TJ, Manning ME, Lawo JP, Machnig T, et al. Indirect comparison of intra­venous vs. subcutaneous Cl-inhibitor placebo-controlled trials for routine prevention of hereditary angioedema attacks. Allergy Asthma Clin lmmunol. 2019;15:13. doi: 10.1186/s13223-019-0328-3

Li HH, Zuraw B, Longhurst HJ, Cicardi M, Bork K, Baker J, et al, Subcutaneous C1 inhibitor for prevention of attacks of hereditary angioedema: additional outcomes and subgroup analysis of a placebo-controlled randomized study. Allergy, Asthma Clin lmmunol. 2019; 15:49. doi: 10.1186/s13223-019-0362-1

Aygören-Pürsün E, Bygum A, Grivcheva-Panovska V, Magerl M, Graff J, Steiner UC, et al, Oral plasma kallikrein inhibitor for prophylaxis in hereditary angioedema. N Engl J Med. 2018;379(4):352-362. doi: 10.1056/NEJMoa1716995

Zuraw B, Lumry WR, Johnston DT, Aygören-Pürsün E, Banerji A, Bernstein JA, et al. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial. J Allergy Clin Immunol. 2021;148(1):164-172.e9. doi: 10.1016/j.jaci.2020.10.015

Wedner HJ, Aygören-Pürsün E, Bernstein J, Craig T, Gower R, Jacobs JJ, et al. Randomized trial of the efficacy and safety of berotralstat (BCX7353) as an oral prophylactic therapy for hereditary angioedema: results of APeX-2 through 48 weeks (Part 2) J Allergy Clin Immunol Pract. 2021;9(6):2305-2314.e4. doi: 10.1016/j.jaip.2021.03.057

U.S. Food and Drug Administration. Center for Biologics Evaluation and Research (CBER). Voice of the patient: hereditary angioedema. [Internet]. May 2018. [Accessed February 7, 2021]. Available from:—Hereditary-Angioedema.pdf.

Farkas H, Stobiecki M, Peter J, Kinaciyan T, Mauer M, Aygören-Pürsün E, et al., Long‐term safety and effectiveness of berotralstat for hereditary angioedema: the open‐label APeX‐S study Clin Transl Allergy. 2021;11(4):e12035. doi: 10.1002/clt2.12035




How to Cite

Ohayon J. Berotralstat: A data review of a novel oral medication for the treatment of hereditary angioedema. Can Allergy Immunol Today [Internet]. 2024 Jan. 23 [cited 2024 Jun. 14];4(s01-2):2–8. Available from:




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