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NICE guidance - Berotralstat for preventing recurrent attacks of hereditary angioedema

Authoring team

NICE state (1):

  • Berotralstat is recommended as an option for preventing recurrent attacks of hereditary angioedema in people 12 years and older, only if:
    • they have at least 2 attacks per month, and
    • it is stopped if the number of attacks per month does not reduce by at least 50% after 3 months

Notes:

  • hereditary angioedema (HAE) is due to C1 inhibitor (C1-INH) deficiency
  • (HAE-C1-INH) is a genetic disease characterized by recurrent attacks of subcutaneous and/or submucosal swelling (2)
    • (HAE-C1-INH) is an autosomal-dominant disorder resulting from mutations in the SERPING1 gene
    • HAE-C1-INH is caused by either quantitative deficiencies or dysfunctional production of C1-INH, leading to uncontrolled plasma kallikrein activity, excessive release of bradykinin, and consequent angioedema
    • attacks are unpredictable, often associated with significant morbidity, and potentially fatal as a result of asphyxiation due to laryngeal angioedema (3)
      • mean frequency of attacks in untreated patients is approximately every 2 weeks
      • with individual attacks lasting 3 to 5 days before fully resolving
      • combination of asphyxiation risk, unpredictability, severity, and frequency of attacks justify prophylactic treatment; the possibility of passing HAE-C1-INH to the next generation contributes to a severe disease burden with markedly reduced quality of life
  • berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE)
    • study evidence shows that both berotralstat doses, 150 and 110 mg once daily, were generally well tolerated. Effectiveness results support the durability and robustness of berotralstat as prophylactic therapy in patients with HAE (2)

Reference:

  • NICE (October 2021). Berotralstat for preventing recurrent attacks of hereditary angioedema
  • Farkas H, Stobiecki M, Peter J, 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
  • Zuraw B 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 Jul;148(1):164-172.e9. doi: 10.1016/j.jaci.2020.10.015. Epub 2020 Oct 21. PMID: 33098856

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