Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Indian Science
  4. Volume 2, Issue 1
  5. Article
Volume 2, Issue 1
  • ISSN: 2210-299X
  • E-ISSN: 2210-3007
file format pdf download PDF
file format text download EPUB
side by side viewer icon HTML

Abstract

Tezepelumab is a first-in-class human IgG2λ monoclonal antibody used to treat severe, uncontrolled asthma. Tezepelumab acts by hindering the action of thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine that triggers an immunological response by binding to TSLP and thereby preventing its binding with the TSLP receptor complex. TSLP has a critical role in Th2 immunity and plays an important role in the pathogenesis of asthma because it stimulates the production of Th2-associated inflammatory mediators, such as interleukin-4, interleukin-5, interleukin-9, and interleukin-13. It is the first biologic with no phenotypic or biomarker restrictions that has been approved for use in severe asthma. Tezepelumab is indicated in severe, uncontrolled asthma patients due to its safety, tolerability, and efficacy. Adults with severe, uncontrolled asthma experienced considerably lower annualised asthma exacerbation rates (AAERs) when administered with tezepelumab compared to a placebo. These preliminary results indicated that the TSLP-induced release of T2 inflammatory mediators may be reduced, and the sustained inhibition was maintained over a 52-week treatment period. In this review, we have summarised various phase III clinical trials and the mechanism of action of tezepelumab in severe, uncontrolled asthma.

© 2024 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Loading

Article metrics loading...

/content/journals/cis/10.2174/012210299X258665231205115939
2023-12-12
2025-01-04

  • From This Site

    /content/journals/cis/10.2174/012210299X258665231205115939
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/cis/2/1/CIS-2-E2210299X258665.html?itemId=/content/journals/cis/10.2174/012210299X258665231205115939&mimeType=html&fmt=ahah

References

  1. 2022 GINA Main Report - Global Initiative for Asthma - GINA.2022Available from: https://ginasthma.org/gina-reports/
  2. Dorey-SteinZ.L. ShenoyK.V. Tezepelumab as an merging therapeutic option for the treatment of severe asthma: Evidence to ate.Drug Des. Devel. Ther.20211533133810.2147/DDDT.S25082533536746
     [Google Scholar]
  3. Menzies-GowA. WechslerM.E. BrightlingC.E. Unmet need in severe, uncontrolled asthma: can anti-TSLP therapy with tezepelumab provide a valuable new treatment option?Respir. Res.202021126810.1186/s12931‑020‑01505‑x33059715
     [Google Scholar]
  4. MeteranH. TønnesenL.L. SivapalanP. IngebrigtsenT.S. JensenJ.U.S. Recent developments in the management of severe asthma.Breathe202218121017810.1183/20734735.0178‑202136338257
     [Google Scholar]
  5. Menzies-GowA. SteenkampJ. SinghS. ErhardtW. RowellJ. RaneP. MartinN. LlanosJ.P. QuintonA. Tezepelumab compared with other biologics for the treatment of severe asthma: A systematic review and indirect treatment comparison.J. Med. Econ.202225167969010.1080/13696998.2022.207419535570578
     [Google Scholar]
  6. MateraM.G. RoglianiP. CalzettaL. CazzolaM. Inhibitors for asthma: Current status and future prospects.Drugs2020805449458
     [Google Scholar]
  7. McGregorM.C. KringsJ.G. NairP. CastroM. Role of biologics in asthma.Am. J. Respir. Crit. Care Med.2019199443344510.1164/rccm.201810‑1944CI30525902
     [Google Scholar]
  8. CalhounW.J. ChuppG.L. The new era of add-on asthma treatments: Where do we stand?Allergy Asthma Clin. Immunol.20221814210.1186/s13223‑022‑00676‑035598022
     [Google Scholar]
  9. ChengS.L. Molecular targets for biological therapies of severe asthma: Focus on benralizumab and tezepelumab.Life202111874410.3390/life1108074434440488
     [Google Scholar]
  10. PerikleousE.P. SteiropoulosP. NenaE. ParaskakisE. Biologic therapies in pediatric asthma.J. Pers. Med.202212699910.3390/jpm12060999
     [Google Scholar]
  11. AndoK. FukudaY. TanakaA. SagaraH. Comparative efficacy and safety of tezepelumab and other biologics in patients with inadequately controlled asthma according to thresholds of type 2 inflammatory biomarkers: A systematic review and network meta-analysis.Cells202211581910.3390/cells1105081935269440
     [Google Scholar]
  12. MathurS. HillJ. AmbroseC. MartinN. Llanos-AckertJ.P. MartinN. ColiceG. Effect of tezepelumab in patients with severe, uncontrolled asthma by age of onset, allergic status, and eosinophilic phenotype.J. Allergy Clin. Immunol.20231512AB1710.1016/j.jaci.2022.12.057
     [Google Scholar]
  13. AdamD.N. GooderhamM.J. BeeckerJ.R. HongC.H. JackC.S. JainV. Expert consensus on the systemic treatment of atopic dermatitis in special populations.J Eur Acad Dermatol Venereol.202337611351148
     [Google Scholar]
  14. Tezspire (tezepelumab) approved in the US for severe asthma.Available from: https://www.astrazeneca.com/media-centre/press-releases/2021/tezspire-tezepelumab-approved-in-the-us-for-severe-asthma.html
  15. Menzies-GowA. CorrenJ. BourdinA. ChuppG. IsraelE. WechslerM.E. BrightlingC.E. GriffithsJ.M. HellqvistÅ. BowenK. KaurP. AlmqvistG. PonnarambilS. ColiceG. Tezepelumab in adults and adolescents with severe, uncontrolled asthma.N. Engl. J. Med.2021384191800180910.1056/NEJMoa203497533979488
     [Google Scholar]
  16. Tezepelumab Granted Breakthrough Therapy Designation By US FDA For The Treatment Of Patients With Severe Asthma Without An Eosinophilic Phenotype.Available from: https://www.amgen.com/newsroom/press-releases/2018/09/tezepelumab-granted-breakthrough-therapy-designation-by-us-fda-for-the-treatment-of-patients-with-severe-asthma-without-an-eosinophilic-phenotype
  17. Tezepelumab granted Orphan Drug Designation in the US for eosinophilic esophagitis.Available from: https://www.astrazeneca.com/media-centre/press-releases/2021/tezepelumab-granted-orphan-drug-designation-in-the-us-for-eosinophilic-esophagitis.html
  18. Tezspire recommended for approval in the EU by CHMP for the treatment of severe asthma.Available from: https://www.astrazeneca.com/media-centre/press-releases/2022/tezspire-recommended-for-approval-in-the-eu-by-chmp.html
  19. Tezspire approved in the EU for the treatment of severe asthma.Available from: https://www.astrazeneca.com/media-centre/press-releases/2022/tezspire-approved-in-the-eu-for-the-treatment-of-severe-asthma.html
  20. Tezspire approved in Japan for the treatment of severe asthma.Available from: https://www.astrazeneca.com/media-centre/press-releases/2022/tezspire-approved-in-japan-for-severe-asthma.html
  21. Tezepelumab significantly reduced asthma exacerbations for a broad population of patients with severe uncontrolled asthma.Available from: https://www.astrazeneca.com/media-centre/press-releases/2017/tezepelumab-significantly-reduced-asthma-exacerbations-for-a-broad-population-of-patients-with-severe-uncontrolled-asthma-06092017.html#
  22. MaroneG. SpadaroG. BraileM. PotoR. CriscuoloG. PahimaH. LoffredoS. Levi-SchafferF. VarricchiG. Tezepelumab: A novel biological therapy for the treatment of severe uncontrolled asthma.Expert Opin. Investig. Drugs2019281193194010.1080/13543784.2019.167265731549891
     [Google Scholar]
  23. BelE.H. Moving upstream — Anti-TSLP in persistent uncontrolled asthma.N. Engl. J. Med.20173771098999110.1056/NEJMe170951928877024
     [Google Scholar]
  24. CorrenJ. AmbroseC.S. SałapaK. RosetiS.L. GriffithsJ.M. ParnesJ.R. ColiceG. Efficacy of tezepelumab in patients with severe, uncontrolled asthma and perennial allergy.J. Allergy Clin. Immunol. Pract.202191243344342.e610.1016/j.jaip.2021.07.04534358701
     [Google Scholar]
  25. LyN. ZhengY. GriffithsJ.M. van der MerweR. AgoramB. ParnesJ.R. RoskosL. Pharmacokinetic and pharmacodynamic modeling of tezepelumab to guide phase 3 dose selection for patients with severe asthma.J. Clin. Pharmacol.202161790191210.1002/jcph.180333368307
     [Google Scholar]
  26. MatucciA. MichelettoC. VultaggioA. Severe asthma and biologics: Managing complex patients.J. Investig. Allergol. Clin. Immunol.202333316817810.18176/jiaci.085636059229
     [Google Scholar]
  27. FeistJ. LipariM. Kale-PradhanP. Tezepelumabin the treatment of uncontrolled severe asthma.Ann Pharmacother.20225716270
     [Google Scholar]
  28. HoyS.M. Tezepelumab: First approval.Drugs202282446146810.1007/s40265‑022‑01679‑235184265
     [Google Scholar]
  29. MedWatch: The FDA safety information and adverse event reporting program.Available from: www.fda.gov/medwatch
  30. ParnesJ. MolfinoN.A. ColiceG. MartinU. CorrenJ. Menzies-GowA. Targeting TSLP in Asthma.J. Asthma Allergy20221574976510.2147/JAA.S27503935685846
     [Google Scholar]
  31. Menzies-GowA. ColiceG. GriffithsJ.M. AlmqvistG. PonnarambilS. KaurP. RubertoG. BowenK. HellqvistÅ. MoM. Garcia GilE. NAVIGATOR: A phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma.Respir. Res.202021126610.1186/s12931‑020‑01526‑633050934
     [Google Scholar]
  32. Menzies-GowA. BourdinA. ChuppG. IsraelE. HellqvistÅ. HunterG. Effect of tezepelumab on healthcare utilization in patients with severe, uncontrolled asthma: The NAVIGATOR study.Ann Allergy Asthma Immunol20231313343348.e2
     [Google Scholar]
  33. CorrenJ. Menzies-GowA. ChuppG. IsraelE. KornS. CookB. AmbroseC.S. HellqvistÅ. RosetiS.L. MolfinoN.A. LlanosJ.P. MartinN. BowenK. GriffithsJ.M. ParnesJ.R. ColiceG. Efficacy of tezepelumab in severe, uncontrolled asthma: Pooled analysis of the PATHWAY and NAVIGATOR clinical trials.Am. J. Respir. Crit. Care Med.20232081132410.1164/rccm.202210‑2005OC37015033
     [Google Scholar]
  34. WechslerM.E. ColiceG. GriffithsJ.M. AlmqvistG. SkärbyT. PiechowiakT. KaurP. BowenK. HellqvistÅ. MoM. Garcia GilE. SOURCE: A phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma.Respir. Res.202021126410.1186/s12931‑020‑01503‑z33050928
     [Google Scholar]
  35. Menzies-GowA. WechslerM.E. BrightlingC.E. KornS. CorrenJ. IsraelE. ChuppG. BednarczykA. PonnarambilS. CaveneyS. AlmqvistG. GołąbekM. SimonssonL. LawsonK. BowenK. ColiceG. HetzelJ.L. FitermanJ. Souza MachadoA. AntilaM.A. LimaM.A. MinamotoS.E.T. BlancoD.C. BezerraP.G.M. HouleP-A. LemiereC. MelenkaL.S. LeighR. MitchellP. AneesS. PekB. ChouinardG. CheemaA.S. YangW.H-C. PhilteosG. ChanezP. BourdinA. DevouassouxG. TailleC. De BlayF. LeroyerC. BeurnierA. GarciaG. GirodetP-O. BlancF-X. MagnanA. WaninS. JustJ. LindeR. ZielenS. FörsterK. GeßnerC. JandlM. BuhlR.O. KornS. KornmannM.O. LinnhoffA. Ludwig-SengpielA. EhlersM. SchmollerT. SteffenH. HoffmannM. KirschnerJ. SchmidtO. WelteT. TemmeH. WandO. Bar-ShaiA. IzbickiG. BerkmanN. FinkG. ShitritD. AdirY. KunaP. RewerskaB. Pisarczyk-BogackaE. KurbachevaO. MikhailovS.L. VasilevM. EmelyanovA. WaliS. AlbannaA. van Zyl-SmitR. AbdullahI. AbdullahI. BernhardiD. HoosenF. IrusenE. KallaI. LakhaD. MithaE. NaidooV. NellH. PadayacheeT. ReddyJ. PetrickF. van der WaltE. VawdaZ.F.A. ParkH-S. LeeS.H. KimM-K. ParkJ-W. ChoY.S. LeeB.J. ChangY-S. ParkC-S. LeeK.H. LeeS.Y. YoonH.K. SohnK.H. ParkM.J. MinK.H. ChoY.J. ParkH.K. LeeY.C. LeeJ. SheuC-C. TuC-Y. LeeK-Y. BavbekS. GemiciogluB. EdigerD. KalkanI.K. MakieievaN. OstrovskyyM. Dytyatkovs’kaY. MostovoyY.M. LebedK. YakovenkoO. AdamsA. MooringT. TorresL.Jr SextonM. ThompsonE. BernsteinJ.A. LisiP. ChappelC.M. ColeJ. GreenwaldG.I. JonesC. KleinR.M. PhamD.N. SpangenthalS. WeinsteinS.F. WindomH.H. KaoN.L. LeongM.A. MehtaV. MooreW.C. BhatS. AishB. MeltzerS.M. CorrenJ. MossM.H. KerwinE.M. DelgadoJ.P. LucksingerG.H. ThompsonC.A. ChuppG. AlpizarS.A. VadgamaS.V. ZafarZ. JacobsJ.S. LugogoN.J. JainN. SherL.D. AndrawisN.S. FuentesD. BorenE.J. GonzalezE.G. TalrejaN. DurraniS.S. IsraelE. SekhsariaS. DeLeonS. ShuklaM. Totszollosy TarpayM.M. FakihF. HudesG. TillinghastJ.P. KorenblatP.E. ShenoyK. QueL. KureishyS.A. UmehF.C. NguyenV.N. ChuH.T. NguyenT.T.D. Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): A randomised, placebo-controlled extension study.Lancet Respir. Med.202311542543810.1016/S2213‑2600(22)00492‑136702146
     [Google Scholar]
  36. KuriharaM. KabataH. IrieM. FukunagaK. Current summary of clinical studies on anti-TSLP antibody, Tezepelumab, in asthma.Allergol. Int.2023721243010.1016/j.alit.2022.11.00636470789
     [Google Scholar]
  37. ShinkaiM. EbisawaM. FukushimaY. TakeuchiS. OkadaH. TokiyoT. HayashiN. TakikawaM. ColiceG. AlmqvistG. One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: Results of the NOZOMI study.J. Asthma202360361662410.1080/02770903.2022.208230935707873
     [Google Scholar]
  38. CorrenJ. AmbroseC.S. GriffithsJ.M. HellqvistÅ. LindsleyA.W. LlanosJ.P. ColiceG. Menzies-GowA. Efficacy of tezepelumab in patients with evidence of severe allergic asthma: Results from the phase 3 NAVIGATOR study.Clin. Exp. Allergy202353441742810.1111/cea.1425636507576
     [Google Scholar]
  39. WechslerM.E. Menzies-GowA. BrightlingC.E. KunaP. KornS. WelteT. GriffithsJ.M. SałapaK. HellqvistÅ. AlmqvistG. LalH. KaurP. SkärbyT. ColiceG. CambursanoV.H. FernandezM.J. ScherbovskyF.D. YanezA. TolcachierA.J. StokA.M. VerraF.J.B. KornS. ForsterK. RolkeM. Ludwig-SengpielA. SchmollerT. SchmidtO. Milger-KneidingerK. HoffmannM. TemmeH. LinnhoffA. WelteT. KirschnerJ. KunaP. RewerskaB. Pisarczyk-BogackaE. Haak LeeS. Jae LeeB. ParkH-W. ParkJ-W. Young LeeS. Sook ChoY. Ho LeeK. BavbekS. GemiciogluB. EdigerD. Koca KalkanI. HantaI. YorganciogluA. DytyatkovsKaY. MostovoyY.M. LebedK. YakovenkoO. BernsteinD.I. TillinghastJ.P. QueL. MadisonJ. RambasekT. ShenoyK. ThompsonC.A. ChappelC.M. HudesG. SorialE. KureishyS.A. RehmanS.M. LugogoN. GonzalezE.G. UmehF.C. BorenE.J. SigmonJ. IsmailH. MohanA. BansalS. KaelinT.D. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): A randomised, placebo-controlled, phase 3 study.Lancet Respir. Med.202210765066010.1016/S2213‑2600(21)00537‑335364018
     [Google Scholar]
  40. Menzies-GowA. PonnarambilS. DownieJ. BowenK. HellqvistÅ. ColiceG. DESTINATION: A phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma.Respir. Res.202021127910.1186/s12931‑020‑01541‑733087119
     [Google Scholar]
  41. MurrisonL.B. RenX. PreusseK. HeH. KronerJ. ChenX. JenkinsS. JohanssonE. BiaginiJ.M. WeirauchM.T. KopanR. MartinL.J. KhuranaH.G.K. TSLP disease-associated genetic variants combined with airway TSLP expression influence asthma risk.J. Allergy Clin. Immunol.20221491798810.1016/j.jaci.2021.05.03334111451
     [Google Scholar]
  42. VarricchiG. PecoraroA. MaroneG. CriscuoloG. SpadaroG. GenoveseA. MaroneG. Thymic stromal lymphopoietin isoforms, inflammatory disorders, and cancer.Front. Immunol.20189JUL159510.3389/fimmu.2018.0159530057581
     [Google Scholar]
  43. ModenaBD DoroudchiA PatelP SathishV Leveraging genomics to uncover the genetic, environmental and age-related factors leading to asthma.Genomic and Precision Medicine: Infectious and Inflammatory Disease.2019133138110.1016/B978‑0‑12‑801496‑7.00018‑6
     [Google Scholar]
  44. WestE.E. KashyapM. LeonardW.J. TSLP: A key regulator of asthma pathogenesis.Drug Discov. Today Dis. Mech.201293-4e83e8810.1016/j.ddmec.2012.09.00324348685
     [Google Scholar]
  45. PlazaV. CañeteC. DomingoC. MartínezR.C. MuñozX. Efficacy and potential positioning of tezepelumab in the treatment of severe asthma.Open Respiratory Archives20235210023110.1016/j.opresp.2022.10023137496871
     [Google Scholar]
  46. MarkovićI. SavvidesS.N. Modulation of signaling mediated by tslp and il-7 in inflammation, autoimmune diseases, and cancer.Front. Immunol.202011155710.3389/fimmu.2020.0155732849527
     [Google Scholar]
  47. PelaiaC. PelaiaG. CrimiC. MaglioA. GallelliL. TerraccianoR. VatrellaA. Tezepelumab: A potential new biological therapy for severe refractory asthma.Int. J. Mol. Sci.2021229436910.3390/ijms2209436933922072
     [Google Scholar]
  48. MateraM.G. OraJ. RoglianiP. CazzolaM. An overview of the preclinical discovery and development of tezepelumab for the treatment of asthma.Expert Opin. Drug Discov.202318995196310.1080/17460441.2023.223088537387523
     [Google Scholar]
  49. Dorey-SteinZ.L. ShenoyK.V. Tezepelumab as an emerging therapeutic option for the treatment of severe asthma: evidence to date.Drug Des. Devel. Ther.20211533133810.2147/DDDT.S25082533536746
     [Google Scholar]
  50. KogutS.J. CampbellJ.D. PearsonS.D. The influence of US drug price dynamics on cost-effectiveness analyses of biologics.Value Health202326337838310.1016/j.jval.2022.12.01036566884
     [Google Scholar]
  51. HabashM. GuiangH. MayersI. QuintonA. VuongV. DineenA. SinghS. GibsonD. TurnerA.P. Cost-effectiveness of tezepelumab in Canada for severe asthma.J. Med. Econ.202326190291410.1080/13696998.2023.223423537417781
     [Google Scholar]
  52. ChagasG.C.L. XavierD. GomesL. Ferri-GuerraJ. OquetR.E.H. Effects of tezepelumab on quality of life of patients with moderate-to-severe, uncontrolled asthma: Systematic review and meta-analysis.Curr. Allergy Asthma Rep.202323628729810.1007/s11882‑023‑01085‑y37191902
     [Google Scholar]
  53. Study to evaluate efficacy and safety of tezepelumab in reducing oral corticosteroid use in adult patients with severe Asthma (WAYFINDER).Patent NCT052748152023
  54. WechslerM.E. Menzies-GowA. BrightlingC.E. MartinN. CookB. KabelisP. SUNRISE: A phase 3, parallel-group study to evaluate the efficacy and safety of tezepelumab in reducing OCS use in OCS-dependent patients with severe asthma.A31 GLOBAL AND ENVIRONMENTAL INFLUENCES IN ASTHMA.American Thoracic Society2023A1295A129510.1164/ajrccm‑conference.2023.207.1_MeetingAbstracts.A1295
     [Google Scholar]
  55. Study to evaluate the pharmacokinetics of tezepelumab in children with asthma (TRAILHEAD)Patent NCT046736302022
  56. REVErsing airway remodelling with tezepelumab (REVERT).Patent NCT056518412023
  57. Tezepelumab COPD exacerbation study (COURSE).Patent NCT040391132023
  58. Efficacy and safety of tezepelumab in participants with severe chronic rhinosinusitis with nasal polyposis (WAYPOINT).Patent NCT048519642023
  59. RindD.M. McQueenR.B. Herron-SmithS. Herce-HagiwaraB. GutierrezE. CampbellJ.D. FluetschN. PearsonS.D. The effectiveness and value of tezepelumab for severe asthma.J. Manag. Care Spec. Pharm.202228557758010.18553/jmcp.2022.28.5.57735471071
     [Google Scholar]
  60. WilliamsD.M. The potential promise and challenge for tezepelumab as a biologic therapy for severe asthma.J. Manag. Care Spec. Pharm.202228558158310.18553/jmcp.2022.28.5.58135471066
     [Google Scholar]
/content/journals/cis/10.2174/012210299X258665231205115939
Loading
New Drug for Management of Severe Uncontrolled Asthma: Tezepelumab
Curr. Indian Sci. 2, E2210299X258665 (2024); https://doi.org/10.2174/012210299X258665231205115939
/content/journals/cis/10.2174/012210299X258665231205115939
/content/journals/cis/10.2174/012210299X258665231205115939
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Airway hyperresponsiveness; Allergy; Asthma; Inflammation; Remodelling; Thymic stromal lymphopoietin

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test