38
Views
0
CrossRef citations to date
0
Altmetric
Original Research

Safety, pharmacokinetics and pharmacodynamics of SHR-1703, an innovative long-acting anti-interleukin-5 monoclonal antibody, in healthy subjects: a randomized, double-blind, dose-escalation, placebo-controlled phase I study

, , , , &
Received 20 Mar 2024, Accepted 24 May 2024, Published online: 03 Jun 2024

References

  • Klion AD, Ackerman SJ, Bochner BS. Contributions of eosinophils to human health and disease. Annu Rev Pathol. 2020 Jan 24;15(1):179–209. doi: 10.1146/annurev-pathmechdis-012419-032756
  • Rodrigo-Muñoz JM, Gil-Martínez M, Sastre B, et al. Emerging evidence for pleiotropism of eosinophils. Int J Mol Sci. 2021 Jun 30;22(13):7075. doi: 10.3390/ijms22137075
  • Valent P, Klion AD, Roufosse F, et al. Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes. Allergy. 2023 Jan;78(1):47–59. doi: 10.1111/all.15544
  • Del Pozo V, Bobolea I, Rial MJ, et al. Expert consensus on the use of systemic glucocorticoids for managing eosinophil-related diseases. Front Immunol. 2024;14:1310211. doi: 10.3389/fimmu.2023.1310211
  • Jackson DJ, Akuthota P, Roufosse F. Eosinophils and eosinophilic immune dysfunction in health and disease. Eur Respir Rev. 2022 Mar 31;31(163):210150. doi: 10.1183/16000617.0150-2021
  • Bochner BS, Gleich GJ. What targeting eosinophils has taught us about their role in diseases. J Allergy Clin Immunol. 2010 Jul;126(1):16–25; quiz 26–7. doi: 10.1016/j.jaci.2010.02.026
  • Tao Z, Zhu H, Zhang J, et al. Recent advances of eosinophils and its correlated diseases. Front Public Health. 2022;10:954721. doi: 10.3389/fpubh.2022.954721
  • Khatri S, Moore W, Gibson PG, et al. Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2019 May;143(5):1742–1751.e7. doi: 10.1016/j.jaci.2018.09.033
  • Yancey SW, Keene ON, Albers FC, et al. Biomarkers for severe eosinophilic asthma. J Allergy Clin Immunol. 2017 Dec;140(6):1509–1518. doi: 10.1016/j.jaci.2017.10.005
  • Global Initiative for Asthma. Difficult-to-treat & severe asthma in adolescent and adult patients. Available from: https://ginasthma.org/wp-content/uploads/2023/09/GINA-Severe-Asthma-Guide-2023-WEB-WMS.pdf
  • Global Initiative for Asthma. Global strategy for asthma management and prevention (2023 update). Available from: https://ginasthma.org/wp-content/uploads/2023/07/GINA-2023-Full-report-23_07_06-WMS.pdf
  • Agache I, Rocha C, Beltran J, et al. Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: a systematic review for the EAACI guidelines - recommendations on the use of biologicals in severe asthma. Allergy. 2020 May;75(5):1043–1057. doi: 10.1111/all.14235
  • Pavord ID, Bel EH, Bourdin A, et al. From DREAM to REALITI-A and beyond: Mepolizumab for the treatment of eosinophil-driven diseases. Allergy. 2022 Mar;77(3):778–797. doi: 10.1111/all.15056
  • Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1189–1197. doi: 10.1056/NEJMoa1403291
  • Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid-sparing effect of Benralizumab in severe asthma. N Engl J Med. 2017 Jun 22;376(25):2448–2458. doi: 10.1056/NEJMoa1703501
  • Pelaia C, Crimi C, Pelaia G, et al. Real-life evaluation of mepolizumab efficacy in patients with severe eosinophilic asthma, according to atopic trait and allergic phenotype. Clin Exp Allergy. 2020 Jul;50(7):780–788. doi: 10.1111/cea.13613
  • Moore WC, Kornmann O, Humbert M, et al. Stopping versus continuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study). Eur Respir J. 2022 Jan;59(1):2100396. doi: 10.1183/13993003.00396-2021
  • Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2017 May 18;376(20):1921–1932. doi: 10.1056/NEJMoa1702079
  • Dellon ES, Peterson KA, Mitlyng BL, et al. Mepolizumab for treatment of adolescents and adults with eosinophilic oesophagitis: a multicentre, randomised, double-blind, placebo-controlled clinical trial. Gut. 2023 Oct;72(10):1828–1837. doi: 10.1136/gutjnl-2023-330337
  • Gelhorn HL, Balantac Z, Ambrose CS, et al. Patient and physician preferences for attributes of biologic medications for severe asthma. Patient Prefer Adherence. 2019;13:1253–1268. doi: 10.2147/PPA.S198953
  • Bever A, Dunne J, Reynolds J, et al. Exploring perceptions of biologic therapies: a qualitative study among Canadians living with severe asthma. Adv Ther. 2024 Feb 13;41(4):1401–1418. doi: 10.1007/s12325-024-02803-2
  • Zhang M, Carter C, Olson WH, et al. Patient preference for dosing frequency based on prior biologic experience. J Drugs Dermatol. 2017 Mar 1;16(3):220–226.
  • Yu XQ, Robbie GJ, Wu Y, et al. Safety, tolerability, and pharmacokinetics of MEDI4893, an investigational, extended-half-life, anti-staphylococcus aureus alpha-toxin human monoclonal antibody, in healthy adults. Antimicrob Agents Chemother. 2017 Jan;61(1). doi: 10.1128/AAC.01020-16
  • Robbie GJ, Criste R, Dall’acqua WF, et al. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother. 2013 Dec;57(12):6147–6153. doi: 10.1128/AAC.01285-13
  • Dall’acqua WF, Kiener PA, Wu H. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem. 2006 Aug 18;281(33):23514–23524. doi: 10.1074/jbc.M604292200
  • Gershuny V, Sun Q, Schrieber SJ, et al. Considerations for use of pharmacodynamic biomarkers to support biosimilar development - (II) a randomized trial with IL-5 antagonists. Clin Pharmacol Ther. 2023 Jan;113(1):80–89. doi: 10.1002/cpt.2760
  • Smith BP, Vandenhende FR, DeSante KA, et al. Confidence interval criteria for assessment of dose proportionality. Pharm Res. 2000 Oct;17(10):1278–1283. doi: 10.1023/A:1026451721686
  • Clark AM, Halvorsen MB, Braun TL, et al. USL255 extended-release topiramate: dose-proportional pharmacokinetics and tolerability in healthy volunteers. Epilepsia. 2014 Jul;55(7):1069–1076. doi: 10.1111/epi.12654
  • Smith DA, Minthorn EA, Beerahee M. Pharmacokinetics and pharmacodynamics of mepolizumab, an anti-interleukin-5 monoclonal antibody. Clin Pharmacokinet. 2011 Apr;50(4):215–227. doi: 10.2165/11584340-000000000-00000
  • Singh D, Fuhr R, Bird NP, et al. A Phase 1 study of the long-acting anti-IL-5 monoclonal antibody GSK3511294 in patients with asthma. Br J Clin Pharmacol. 2022 Feb;88(2):702–712. doi: 10.1111/bcp.15002
  • Zeiger RS, Schatz M, Dalal AA, et al. Blood eosinophil count and outcomes in severe uncontrolled asthma: a prospective study. J Allergy Clin Immunol Pract. 2017 Jan;5(1):144–153.e8. doi: 10.1016/j.jaip.2016.07.015
  • Chupp GL, Bradford ES, Albers FC, et al. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med. 2017 May;5(5):390–400. doi: 10.1016/S2213-2600(17)30125-X
  • Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1198–1207. doi: 10.1056/NEJMoa1403290
  • Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012 Aug 18;380(9842):651–659. doi: 10.1016/S0140-6736(12)60988-X
  • U.S. Food and Drug Administration. Summary review. Center for drug evaluation and research. Application number: 761033Orig1s000. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761033Orig1s000SumR.pdf
  • U.S. Food and Drug Administration. Medical review(s). Center for drug evaluation and research. Application number: 125526Orig1s000. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/125526Orig1s000MedR.pdf
  • U.S. Food and Drug Administration. Risk assessment and risk mitigation review(s). Center for drug evaluation and research. Application number: 761033Orig1s000. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761033Orig1s000RiskR.pdf

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.