Skip to main content
SpringerLink
Log in

Bimekizumab: The First Dual Inhibitor of Interleukin (IL)-17A and IL-17F for the Treatment of Psoriatic Disease and Ankylosing Spondylitis

  • Review Article
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Psoriasis is a chronic inflammatory skin disease with significant psychological and physical impact. Over the last few decades, several highly effective target therapies have been developed, leading to a major paradigm shift in the way psoriatic disease is managed. Despite this, a proportion of patients still do not respond or lose response over time. Bispecific antibodies target two different cytokines simultaneously, potentially offering a better disease control. Interleukin (IL)-17A and IL-17F share structural homology and have similar biologic function. IL-17A is classically considered to be the most biologically active, but recent studies have shown that IL-17F is also increased in psoriatic skin and synovial cell in psoriatic arthritis, supporting the rationale for targeting both IL-17A and IL-17F in psoriatic disease. Bimekizumab is the first-in-class monoclonal antibody designed to simultaneously target IL-17A and IL-17F. Bimekizumab is currently in clinical development for psoriasis, psoriatic arthritis, and ankylosing spondylitis, with promising results. In early clinical trials, bimekizumab demonstrated a rapid onset of action, good safety profile, and high tolerability by treated study participants. Long-term results and head-to-head trials comparing bimekizumab with other agents will be crucial to define the role of bimekizumab in the treatment of psoriatic disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Yang Y-W, Keller JJ, Lin H-C. Medical comorbidity associated with psoriasis in adults: a population-based study. Br J Dermatol. 2011;165:1037–43.

    Article  PubMed  Google Scholar 

  2. Takeshita J, Grewal S, Langan SM, Mehta NN, Ogdie A, Van Voorhees AS, et al. Psoriasis and comorbid diseases: epidemiology. J Am Acad Dermatol. 2017;76:377–90.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gudjonsson JE. Elder JT. Psoriasis: epidemiology. Clin Dermatol. 2007;25:535–46.

    Article  PubMed  Google Scholar 

  4. Levin AA, Gottlieb AB, Au S. A comparison of psoriasis drug failure rates and reasons for discontinuation in biologics vs conventional systemic therapies. J Drugs Dermatol. 2014;13:848–53.

    CAS  PubMed  Google Scholar 

  5. Hawkes JE, Yan BY, Chan TC, Krueger JG. Discovery of the IL-23/IL-17 signaling pathway and the treatment of psoriasis. J Immunol. 2018;201:1605–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Silfvast-Kaiser A, Paek SY, Menter A. Anti-IL17 therapies for psoriasis. Expert Opin Biol Ther. 2019;19:45–54.

    Article  CAS  PubMed  Google Scholar 

  7. Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis? Ann Rheum Dis. 2018;77:175–87.

    Article  CAS  PubMed  Google Scholar 

  8. Torres T, Romanelli M, Chiricozzi A. A revolutionary therapeutic approach for psoriasis: bispecific biological agents. Expert Opin Investig Drugs. 2016;25:751–4.

    Article  CAS  PubMed  Google Scholar 

  9. Blauvelt A, Chiricozzi A. The immunologic role of IL-17 in psoriasis and psoriatic arthritis pathogenesis. Clin Rev Allergy Immunol. 2018;55(3):379–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gaffen SL, Jain R, Garg AV, Cua DJ. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol. 2014;14:585–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Puig L. The role of IL 23 in the treatment of psoriasis. Expert Rev Clin Immunol. 2017;13:525–34.

    Article  CAS  PubMed  Google Scholar 

  12. Song X, Qian Y. The activation and regulation of IL-17 receptor mediated signaling. Cytokine. 2013;62:175–82.

    Article  CAS  PubMed  Google Scholar 

  13. Johansen C, Usher PA, Kjellerup RB, Lundsgaard D, Iversen L, Kragballe K. Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Br J Dermatol. 2009;160:319–24.

    Article  CAS  PubMed  Google Scholar 

  14. Gu C, Wu L, Li X. IL-17 family: cytokines, receptors and signaling. Cytokine. 2013;64:477–85.

    Article  CAS  PubMed  Google Scholar 

  15. Brembilla NC, Senra L, Boehncke W-H. The IL-17 family of cytokines in psoriasis: IL-17A and beyond. Front Immunol. 2018;9:1682.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Martin DA, Towne JE, Kricorian G, Klekotka P, Gudjonsson JE, Krueger JG, et al. The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. J Invest Dermatol. 2013;133:17–26.

    Article  CAS  PubMed  Google Scholar 

  17. Kirkham BW, Kavanaugh A, Reich K. Interleukin-17A: a unique pathway in immune-mediated diseases: psoriasis, psoriatic arthritis and rheumatoid arthritis. Immunology. 2014;141:133–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Akimzhanov AM, Yang XO, Dong C. Chromatin remodeling of interleukin-17 (IL-17)-IL-17F cytokine gene locus during inflammatory helper T cell differentiation. J Biol Chem. 2007;282:5969–72.

    Article  CAS  PubMed  Google Scholar 

  19. Wright JF, Bennett F, Li B, Brooks J, Luxenberg DP, Whitters MJ, et al. The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex. J Immunol. 2008;181:2799–805.

    Article  CAS  PubMed  Google Scholar 

  20. Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol. 2009;9:556–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Soderstrom C, Berstein G, Zhang W, Valdez H, Fitz L, Kuhn M, et al. Ultra-sensitive measurement of IL-17A and IL-17F in psoriasis patient serum and skin. AAPS J. 2017;19:1218–22.

    Article  CAS  PubMed  Google Scholar 

  22. Watanabe H, Kawaguchi M, Fujishima S, Ogura M, Matsukura S, Takeuchi H, et al. Functional characterization of IL-17F as a selective neutrophil attractant in psoriasis. J Invest Dermatol. 2009;129:650–6.

    Article  CAS  PubMed  Google Scholar 

  23. Fujishima S, Watanabe H, Kawaguchi M, Suzuki T, Matsukura S, Homma T, et al. Involvement of IL-17F via the induction of IL-6 in psoriasis. Arch Dermatol Res. 2010;302:499–505.

    Article  CAS  PubMed  Google Scholar 

  24. Pantelyushin S, Haak S, Ingold B, Kulig P, Heppner FL, Navarini AA, et al. Rorγt+ innate lymphocytes and γδ T cells initiate psoriasiform plaque formation in mice. J Clin Invest. 2012;122:2252–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hawkes JE, Gudjonsson JE, Ward NL. The snowballing literature on imiquimod-induced skin inflammation in mice: a critical appraisal. J Invest Dermatol. 2017;137:546–9.

    Article  CAS  PubMed  Google Scholar 

  26. Maroof A, Okoye R, Smallie T, Baeten D, Arche S, Simpson C, et al. Bimekizumab dual inhibition of IL-17A and IL-17F provides evidence of IL-17F contribution to chronic inflammation in disease-relevant cells [abstract no. 1571]. Arthritis Rheumatol. 2017;69 (suppl. 10). https://acrabstracts.org/abstract/bimekizumab-dual-inhibition-of-il-17a-and-il-17f-provides-evidence-of-il-17f-contribution-to-chronic-inflammation-in-disease-relevant-cells/. Accessed 1 Mar 2019.

  27. Glatt S, Helmer E, Haier B, Strimenopoulou F, Price G, Vajjah P, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017;83:991–1001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Blair HA. Brodalumab: a review in moderate to severe plaque psoriasis. Drugs. 2018;78:495–504.

    Article  CAS  PubMed  Google Scholar 

  29. Caruso R, Stolfi C, Sarra M, Rizzo A, Fantini MC, Pallone F, et al. Inhibition of monocyte-derived inflammatory cytokines by IL-25 occurs via p38 Map kinase-dependent induction of Socs-3. Blood. 2009;113:3512–9.

    Article  CAS  PubMed  Google Scholar 

  30. Papp KA, Merola JF, Gottlieb AB, Griffiths CEM, Cross N, Peterson L, et al. Dual neutralization of both interleukin 17A and interleukin 17F with bimekizumab in patients with psoriasis: results from BE ABLE 1, a 12-week randomized, double-blinded, placebo-controlled phase 2b trial. J Am Acad Dermatol. 2018;79(277–286):e10.

    Google Scholar 

  31. Blauvelt A, Papp K, Merola J, Gottlieb A, Cross N, Madden C, et al. Dual neutralization of interleukin (IL)-17A and IL-17F with bimekizumab in moderate-to-severe plaque psoriasis: 60-week results from a randomized, double-blinded, phase 2b extension study [abstract]. American Academy of Dermatology (AAD) Annual Meeting; 1–5 Mar 2019; Washington, DC.

  32. Glatt S, Baeten D, Baker T, Griffiths M, Ionescu L, Lawson ADG, et al. Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomised placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation. Ann Rheum Dis. 2018;77:523–32.

    Article  CAS  PubMed  Google Scholar 

  33. UCB. Bimekizumab demonstrates impressive joint and skin responses for psoriatic arthritis patients. https://www.ucb.com/stories-media/Press-Releases/article/Bimekizumab-demonstrates-impressive-joint-and-skin-responses-for-psoriatic-arthritis-patients-nbsp. Accessed 17 Oct 2018.

  34. Ritchlin C, Kavanaugh A, Merola JF, Schett G, Scher J, Warren R, et al. Dual neutralization of IL-17A and IL-17F with bimekizumab in patients with active Psa: results from a 48-week phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study [abstract no. L17]. Arthritis Rheumatol. 2018;70 (suppl 10). https://acrabstracts.org/abstract/dual-neutralization-of-il-17a-and-il-17f-with-bimekizumab-in-patients-with-active-psa-results-from-a-48-week-phase-2b-randomized-double-blind-placebo-controlled-dose-ranging-study/. Accessed 17 Mar 2019.

  35. van der Heijde D, Gensler LS, Deodhar A, Baraliakos X, Poddubnyy D, Farmer MK, et al. Dual neutralisation of il-17a and il-17f with bimekizumab in patients with active ankylosing spondylitis (AS): 12-week results from a phase 2b, randomised, double-blind, placebo-controlled, dose-ranging study [abstract no. LB0001]. Ann Rheum Dis. 2018;77:70. http://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2018-eular.7889. Accessed 17 Mar 2019.

  36. Khatri A, Klünder B, Peloso PM, Othman AA. Exposure–response analyses demonstrate no evidence of interleukin 17A contribution to efficacy of ABT-122 in rheumatoid or psoriatic arthritis. Rheumatology. 2019;58:352–60.

    Article  PubMed  Google Scholar 

  37. Genovese MC, Weinblatt ME, Mease PJ, Aelion JA, Peloso PM, Chen K, et al. Dual inhibition of tumour necrosis factor and interleukin-17A with ABT-122: open-label long-term extension studies in rheumatoid arthritis or psoriatic arthritis. Rheumatology. 2018;57:1972–81.

    Article  CAS  PubMed  Google Scholar 

  38. Genovese MC, Weinblatt ME, Aelion JA, Mansikka HT, Peloso PM, Chen K, et al. ABT-122, a bispecific dual variable domain immunoglobulin targeting tumor necrosis factor and interleukin-17A, in patients with rheumatoid arthritis with an inadequate response to methotrexate: a randomized, double-blind study. Arthritis Rheumatol. 2018;70:1710–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Rademacher J, Poddubnyy D. Emerging drugs for the treatment of axial spondyloarthritis. Expert Opin Emerg Drugs. 2018;23:83–96.

    Article  CAS  PubMed  Google Scholar 

  40. Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, et al. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med. 2015;373:2534–48.

    Article  CAS  PubMed  Google Scholar 

  41. Baeten D, Østergaard M, Wei JC-C, Sieper J, Järvinen P, Tam L-S, et al. Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Ann Rheum Dis. 2018;77:1295–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y, et al. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity. 2009;30:108–19.

    Article  CAS  PubMed  Google Scholar 

  43. Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, et al. Regulation of inflammatory responses by IL-17F. J Exp Med. 2008;205:1063–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Jin W, Dong C. IL-17 cytokines in immunity and inflammation. Emerg Microbes Infect. 2013;2(9):e60.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Babaloo Z, Babaie F, Farhoodi M, Aliparasti MR, Baradaran B, Almasi S, et al. Interleukin-17A and interleukin-17F mRNA expression in peripheral blood mononuclear cells of patients with multiple sclerosis. Iran J Immunol. 2010;7:202–9.

    CAS  PubMed  Google Scholar 

  46. Wedebye Schmidt EG, Larsen HL, Kristensen NN, Poulsen SS, Lynge Pedersen AM, Claesson MH, et al. TH17 cell induction and effects of IL-17A and IL-17F blockade in experimental colitis. Inflamm Bowel Dis. 2013;19:1567–76.

    Article  PubMed  Google Scholar 

  47. Saleh MA, Norlander AE, Madhur MS. Inhibition of interleukin-17A, but not interleukin-17F, signaling lowers blood pressure, and reduces end-organ inflammation in angiotensin II–induced hypertension. JACC Basic Transl Sci. 2016;1:606–16.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Tong Z, Yang XO, Yan H, Liu W, Niu X, Shi Y, et al. A protective role by interleukin-17F in colon tumorigenesis. PLoS One. 2012;7:e34959.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Qian X, Chen H, Wu X, Hu L, Huang Q, Jin Y. Interleukin-17 acts as double-edged sword in anti-tumor immunity and tumorigenesis. Cytokine. 2017;89:34–44.

    Article  CAS  PubMed  Google Scholar 

  50. UCB Biopharma S.P.R.L. A study to evaluate the efficacy and safety of bimekizumab in the treatment of subjects with active psoriatic arthritis (BE COMPLETE) [ClinicalTrials.gov identifier NCT03896581]. National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov. Accessed 30 May 2019.

  51. UCB Biopharma S.P.R.L. A study to test the efficacy and safety of bimekizumab in the treatment of subjects with active psoriatic arthritis (BE OPTIMAL) [ClinicalTrials.gov identifier NCT03895203]. National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov. Accessed 30 May 2019.

  52. UCB Biopharma S.P.R.L. A study to evaluate the efficacy and safety of bimekizumab in subjects with active ankylosing spondylitis (BE MOBILE 2) [ClinicalTrials.gov identifier NCT03928743]. National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov. Accessed 30 May 2019.

  53. UCB Biopharma S.P.R.L. A study to evaluate the efficacy and safety of bimekizumab in subjects with active nonradiographic axial spondyloarthritis (BE MOBILE 1) [ClinicalTrials.gov identifier NCT03928704]. National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov. Accessed 30 May 2019.

  54. UCB Biopharma S.P.R.L. A study to evaluate the efficacy and safety of bimekizumab compared to placebo and an active comparator in adult subjects with moderate to severe chronic plaque psoriasis (BE VIVID) [ClinicalTrials.gov identifier NCT03370133]. National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov. Accessed 30 May 2019.

  55. UCB Biopharma S.P.R.L. A study to evaluate the efficacy and safety of bimekizumab in adult subjects with moderate to severe chronic plaque psoriasis (BE SURE) [ClinicalTrials.gov identifier NCT03412747]. National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov. Accessed 30 May 2019.

  56. UCB Biopharma S.P.R.L. A study to evaluate the efficacy and safety of bimekizumab compared to an active comparator in adult subjects with moderate to severe chronic plaque psoriasis (BE RADIANT) [ClinicalTrials.gov identifier NCT03536884]. National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov. Accessed 30 May 2019.

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, Centro Hospitalar Universitário do Porto, Rua D. Manuel II, s/n, ex-CICAP, 4099-001, Porto, Portugal

    Joel Reis & Tiago Torres

  2. Department of Dermatology, McMaster University, Hamilton, ON, Canada

    Ron Vender

  3. Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal

    Tiago Torres

Authors
  1. Joel Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ron Vender
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tiago Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tiago Torres.

Ethics declarations

Funding

No funding was received that was directly related to this review.

Conflict of interest

Joel Reis has no conflict of interest. Ron Vender has participated in clinical trials, and has received honoraria for acting as a consultant and/or as a speaker at events sponsored by AbbVie, Amgen, Boehringer Ingelheim, Celgene, Galderma, GSK, Janssen, Leo-Pharma, Eli-Lilly, MSD, Novartis, UCB, and Pfizer. Tiago Torres has participated in clinical trials, and has received honoraria for acting as a consultant and/or as a speaker at events sponsored by AbbVie, Amgen, Boehringer Ingelheim, Celgene, Janssen, Leo-Pharma, Eli-Lilly, MSD, Novartis, Pfizer, and Sandoz.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reis, J., Vender, R. & Torres, T. Bimekizumab: The First Dual Inhibitor of Interleukin (IL)-17A and IL-17F for the Treatment of Psoriatic Disease and Ankylosing Spondylitis. BioDrugs 33, 391–399 (2019). https://doi.org/10.1007/s40259-019-00361-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40259-019-00361-6

Search

Navigation