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Drugs

, Volume 79, Issue 16, pp 1777–1784 | Cite as

Lanadelumab: A Review in Hereditary Angioedema

  • Yahiya Y. SyedEmail author
Adis Drug Evaluation

Abstract

Lanadelumab (Takhzyro™), a first-in-class fully human monoclonal antibody against plasma kallikrein, has been approved in several countries, including Australia, Canada, those of the EU, Switzerland and the USA, for the prevention of hereditary angioedema (HAE) attacks in patients aged ≥ 12 years. Subcutaneous lanadelumab significantly reduced HAE attack rates relative to placebo in the pivotal HELP trial. The clinical benefits of lanadelumab were seen regardless of prior long-term prophylaxis use, baseline disease activity, sex or body mass index. Lanadelumab therapy was associated with clinically meaningful improvements in HAE-specific quality of life. Lanadelumab was generally well tolerated. The most common adverse events with lanadelumab were injection-site reactions, which were generally mild and transient. Lanadelumab has a low potential for immunogenicity. It offers the convenience of self-administered subcutaneous injections once every 2 weeks (starting dosage). Currently available data indicate that lanadelumab is an effective, well-tolerated, novel prophylactic option for patients with HAE aged ≥ 12 years.

Notes

Acknowledgements

During the peer review process the manufacturer of lanadelumab was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with Ethical Standards

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Yahiya Y. Syed is a salaried employee of Adis International Ltd/Springer Nature, is responsible for the article content and declares no relevant conflicts of interest.

References

  1. 1.
    Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema—the 2017 revision and update. Allergy. 2018;73(8):1575–96.CrossRefGoogle Scholar
  2. 2.
    Zuraw BL, Banerji A, Bernstein JA, et al. US Hereditary Angioedema Association Medical Advisory Board 2013 recommendations for the management of hereditary angioedema due to C1 inhibitor deficiency. J Allergy Clin Immunol Pract. 2013;1(5):458–67.CrossRefGoogle Scholar
  3. 3.
    Cicardi M, Bork K, Caballero T, et al. Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy. 2012;67(2):147–57.CrossRefGoogle Scholar
  4. 4.
    Kenniston JA, Faucette RR, Martik D, et al. Inhibition of plasma kallikrein by a highly specific active site blocking antibody. J Biol Chem. 2014;289(34):23596–608.CrossRefGoogle Scholar
  5. 5.
    European Medicines Agency. TAKHZYRO 300 mg solution for injection: summary of product characteristics. 2018. https://www.ema.europa.eu. Accessed 20 Sept 2019.
  6. 6.
    Shire. TAKHZYRO™ (lanadelumab-flyo) injection, for subcutaneous use: US prescribing information. 2018. https://www.fda.gov. Accessed 20 Sept 2019.
  7. 7.
    Sexton DJ, Faucette R, Kenniston J, et al. Approaches to estimate plasma kallikrein inhibition levels required for attack prophylaxis in hereditary angioedema [abstract no. 1055]. Allergy. 2017;72(Suppl. 103):596.Google Scholar
  8. 8.
    Chyung Y, Vince B, Iarrobino R, et al. A phase 1 study investigating DX-2930 in healthy subjects. Ann Allergy Asthma Immunol. 2014;113(4):460–6.CrossRefGoogle Scholar
  9. 9.
    Banerji A, Busse P, Shennak M, et al. Inhibiting plasma kallikrein for hereditary angioedema prophylaxis. N Engl J Med. 2017;376(8):717–28.CrossRefGoogle Scholar
  10. 10.
    Cicardi M, Shennak M, Zaragoza-Urdaz RH, et al. Pharmacokinetics and pharmacodynamics of lanadelumab in patients with HAE in the phase 3 HELP study [abstract no. 1428]. Allergy. 2018;73(Suppl. 105):722.Google Scholar
  11. 11.
    Jomphe C, Gosselin N, Marier JF, et al. Potential pharmacodynamic drug interaction between lanadelumab and drugs commonly used in patients with hereditary angioedema [abstract no. T-018]. J Pharmacokinet Pharmacodyn. 2018;45(Suppl. 1):S54–S5.Google Scholar
  12. 12.
    Banerji A, Riedl MA, Bernstein JA, et al. Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: a randomized clinical trial. JAMA. 2018;320(20):2108–21.CrossRefGoogle Scholar
  13. 13.
    Schmaier AH, Bauer KA, Cicardi M, et al. Effect of lanadelumab on coagulation parameters in patients with hereditary angioedema: findings from the phase 3 HELP study [abstract no. 121]. J Allergy Clin Immunol. 2019;143(2 Suppl.):AB41.CrossRefGoogle Scholar
  14. 14.
    Sexton DJ, Brown NJ, Lumry WR, et al. Lanadelumab and cardiovascular risk: findings from the phase 3 HELP study [abstract no. 136]. J Allergy Clin Immunol. 2019;143(2 Suppl.):AB45.CrossRefGoogle Scholar
  15. 15.
    Chang C, Offman E, Marier JF, et al. Population pharmacokinetic analysis of lanadelumab in patients with hereditary angioedema [abstract no. W-002]. J Pharmacokinet Pharmacodyn. 2018;45(Suppl. 1):S90.Google Scholar
  16. 16.
    Inhaber N, Zuraw BL, Marier JF, et al. Relationship between body weight, PK/PD and attack responses following subcutaneous administration of lanadelumab in patients with hereditary angioedema [abstract no. 115]. J Allergy Clin Immunol. 2019;143(2 Suppl.):AB38.Google Scholar
  17. 17.
    Chang C, Offman E, Marier JF, et al. Pharmacokinetic/pharmacodynamic analysis of lanadelumab in patients with hereditary angioedema (HAE) [abstract no. T-019]. J Pharmacokinet Pharmacodyn. 2018;45(Suppl. 1):S55.Google Scholar
  18. 18.
    Zuraw B, Cicardi M, Jacobs J, et al. Lanadelumab exposure during steady state: achievement of effective concentrations in patients in the HELP study [abstract no. P170]. Ann Allergy Asthma Immunol. 2018;121(5 Suppl.):S37–S8.CrossRefGoogle Scholar
  19. 19.
    Wedner HJ, Busse PJ, Banerji A, et al. Modeling and analyses to identify potential dosing regimens of DX-2930 for the long-term prophylaxis of hereditary angioedema [abstract no. 822]. J Allergy Clin Immunol. 2016;137(2 Suppl.):AB252.CrossRefGoogle Scholar
  20. 20.
    Wang Y, Marier JF, Kassir N, et al. Exposure-response analyses of lanadelumab in patients with hereditary angioedema [abstract no. 120]. J Allergy Clin Immunol. 2019;143(2 Suppl.):AB40.CrossRefGoogle Scholar
  21. 21.
    Busse PJ, Tachdjian R, Martinez-Saguer I, et al. Efficacy and safety of lanadelumab for prophylactic treatment in adolescents with hereditary angioedema (HAE) [abstract no. 129]. J Allergy Clin Immunol. 2019;143(2 Suppl.):AB43.CrossRefGoogle Scholar
  22. 22.
    Banerji A, Manning ME, Martinez-Saguer I, et al. Subgroup analyses from the phase 3 HELP study of lanadelumab for the prevention of hereditary angioedema attacks [abstract no. 124]. J Allergy Clin Immunol. 2019;143(2 Suppl.):AB42.CrossRefGoogle Scholar
  23. 23.
    Riedl MA, Anderson JT, Cicardi M, et al. Efficacy of lanadelumab in hereditary angioedema patients switching from C1 inhibitor long-term prophylaxis: interim results from the HELP open-label extension study [abstract no. 112]. J Allergy Clin Immunol. 2019;143(2 Suppl.):AB37.CrossRefGoogle Scholar
  24. 24.
    Jacobs JS, Bernstein J, Davis-Lorton M, et al. Increased response to higher dose lanadelumab in hereditary angioedema patients: exploratory findings from the HELP and HELP OLE studies [abstract no. 114]. J Allergy Clin Immunol. 2019;143(2 Suppl.):AB38.CrossRefGoogle Scholar
  25. 25.
    Riedl M, Bernstein J, Yang W, et al. Lanadelumab reduces HAE attack rate: interim findings from the HELP open-label extension study [abstract no. P168]. Ann Allergy Asthma Immunol. 2018;121(5 Suppl.):S37.CrossRefGoogle Scholar
  26. 26.
    Tachdjian R, Anderson J, Busse P, et al. Lanadelumab efficacy after switching from placebo: results from the HELP and HELP open-label extension studies [abstract no. P171]. Ann Allergy Asthma Immunol. 2018;121(5 Suppl.):S38.CrossRefGoogle Scholar
  27. 27.
    Riedl MA, Bernstein JA, Craig T, et al. An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension. Clin Transl Allergy. 2017;7(36):1–10.Google Scholar
  28. 28.
    National Institute for Health And Care Excellence. Final appraisal document: lanadelumab for preventing recurrent attacks of hereditary angioedema. 2019. https://www.nice.org.uk. Accessed 20 Sept 2019.
  29. 29.
    Agboola F, Lubinga S, Carlson J, et al. The effectiveness and value of lanadelumab and C1 esterase inhibitors for prophylaxis of hereditary angioedema attacks. J Manag Care Spec Pharm. 2019;25(2):143–8.PubMedGoogle Scholar
  30. 30.
    Zuraw BL. Cost-effectiveness of prophylactic medications for the treatment of hereditary angioedema due to C1 inhibitor deficiency: a real-world US perspective. J Manag Care Spec Pharm. 2019;25(2):148–51.PubMedGoogle Scholar
  31. 31.
    Lumry W, Busse P, Lu P, et al. Subcutaneous self-administration of lanadelumab for prophylactic treatment in patients with hereditary angioedema (HAE) [abstract no. P352]. Ann Allergy Asthma Immunol. 2018;121(5 Suppl.):S57.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Springer NatureAucklandNew Zealand

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