Tezepelumab for Severe Asthma: One Drug Targeting Multiple Disease Pathways and Patient Types

References

• Busse WW. Biological treatments for severe asthma: a major advance in asthma care. Allergol Int. 2019;68(2):158–166. doi:10.1016/j.alit.2019.01.004
   PubMedGoogle Scholar
• Menzies-Gow A, Wechsler ME, Brightling CE. Unmet need in severe, uncontrolled asthma: can anti-TSLP therapy with tezepelumab provide a valuable new treatment option? Respir Res. 2020;21(1):268. doi:10.1186/s12931-020-01505-x
   PubMed Web of Science ®Google Scholar
• The global asthma report 2022. Int J Tuberc Lung Dis. 2022;26(1):1–104. doi:10.5588/ijtld.22.1010
   Google Scholar
• Gauvreau GM, Sehmi R, Ambrose CS, Griffiths JM. Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert Opin Ther Targets. 2020;24(8):777–792. doi:10.1080/14728222.2020.1783242
   PubMed Web of Science ®Google Scholar
• Backman H, Jansson SA, Stridsman C, et al. Severe asthma-A population study perspective. Clin Exp Allergy. 2019;49(6):819–828. doi:10.1111/cea.13378
   PubMed Web of Science ®Google Scholar
• Chen S, Golam S, Myers J, Bly C, Smolen H, Xu X. Systematic literature review of the clinical, humanistic, and economic burden associated with asthma uncontrolled by GINA steps 4 or 5 treatment. Curr Med Res Opin. 2018;34(12):2075–2088. doi:10.1080/03007995.2018.1505352
   PubMed Web of Science ®Google Scholar
• Reibman J, Tan L, Ambrose C, et al. Clinical and economic burden of severe asthma among US patients treated with biologic therapies. Ann Allergy Asthma Immunol. 2021;127(3):318–325.e2. doi:10.1016/j.anai.2021.03.015
   PubMed Web of Science ®Google Scholar
• FasenraTM (benralizumab) Prescribing Information. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2023. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761070s000lbl.pdf. Accessed February 26, 2024
   Google Scholar
• Cinqair(R) (reslizumab) Prescribing Information. Teva Pharmaceutical Industries Ltd., Teva Respiratory, LLC: Frazer, PA; 2023. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761033lbl.pdf. Accessed February 26, 2024
   Google Scholar
• Xolair(R) (omalizumab) Prescribing Information. CA: Genentech Inc; 2023. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/103976s5238lbl.pdf. Accessed February 26, 2024
   Google Scholar
• Nucala (mepolizumab) Prescribing Information. PA: GlaxoSmithKline LLC; 2023. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761122s008,125526s019lbl.pdf.Accessed February 26, 2024
   Google Scholar
• Dupixent (dupilumab) Prescribing Information. NJ: Regeneron Pharmaceuticals Inc NY, Sanofi-aventis U.S. LLC; 2023. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761055s040lbl.pdf. Accessed February 26, 2024
   Google Scholar
• Wang E, Wechsler ME, Tran TN, et al. Characterization of severe asthma worldwide: data from the International Severe Asthma Registry. Chest. 2020;157(4):790–804. doi:10.1016/j.chest.2019.10.053
   PubMed Web of Science ®Google Scholar
• Kupczyk M, Dahlen B, Sterk PJ, et al. Stability of phenotypes defined by physiological variables and biomarkers in adults with asthma. Allergy. 2014;69(9):1198–1204. doi:10.1111/all.12445
   PubMed Web of Science ®Google Scholar
• Tran TN, Zeiger RS, Peters SP, et al. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann Allergy Asthma Immunol. 2016;116(1):37–42. doi:10.1016/j.anai.2015.10.027
   PubMed Web of Science ®Google Scholar
• Porsbjerg CM, Sverrild A, Lloyd CM, Menzies-Gow AN, Bel EH. Anti-alarmins in asthma: targeting the airway epithelium with next-generation biologics. Eur Respir J. 2020;56(5):2000260. doi:10.1183/13993003.00260-2020
   PubMed Web of Science ®Google Scholar
• Brusselle GG, Maes T, Bracke KR. Eosinophils in the spotlight: eosinophilic airway inflammation in nonallergic asthma. Nat Med. 2013;19(8):977–979. doi:10.1038/nm.3300
   PubMed Web of Science ®Google Scholar
• Brusselle G, Bracke K. Targeting immune pathways for therapy in asthma and chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2014;11(5):S322–8. doi:10.1513/AnnalsATS.201403-118AW
   PubMedGoogle Scholar
• Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol. 2015;16(1):45–56. doi:10.1038/ni.3049
   PubMed Web of Science ®Google Scholar
• Plaza V, Cañete C, Domingo C, Martínez Rivera C, Muñoz X. Efficacy and potential positioning of tezepelumab in the treatment of severe asthma. Open Respir Arch. 2023;5(2):100231. doi:10.1016/j.opresp.2022.100231
   PubMedGoogle Scholar
• Roan F, Obata-Ninomiya K, Ziegler SF. Epithelial cell-derived cytokines: more than just signaling the alarm. J Clin Invest. 2019;129(4):1441–1451. doi:10.1172/JCI124606
   PubMed Web of Science ®Google Scholar
• Varricchi G, Pecoraro A, Marone G, et al. Thymic stromal lymphopoietin isoforms, inflammatory disorders, and cancer. Front Immunol. 2018;9:1595. doi:10.3389/fimmu.2018.01595
   PubMed Web of Science ®Google Scholar
• Tezpire(TM) (tezepelumab-ekko) Prescribing Information. CA: Amgen Inc; 2023. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761224s000lbl.pdf. Accessed February 26, 2024
   Google Scholar
• Corren J, Parnes JR, Wang L, et al. Tezepelumab in adults with uncontrolled Asthma. N Engl J Med. 2017;377(10):936–946. doi:10.1056/NEJMoa1704064
   PubMed Web of Science ®Google Scholar
• Menzies-Gow A, Colice G, Griffiths JM, et al. 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. 2020;21(1):266. doi:10.1186/s12931-020-01526-6
   PubMed Web of Science ®Google Scholar
• Menzies-Gow A, Corren J, Bourdin A, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. 2021;384(19):1800–1809. doi:10.1056/NEJMoa2034975
   PubMed Web of Science ®Google Scholar
• Wechsler ME, Colice G, Griffiths JM, et al. 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. 2020;21(1):264. doi:10.1186/s12931-020-01503-z
   PubMed Web of Science ®Google Scholar
• Wechsler ME, Menzies-Gow A, Brightling CE, et al. 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. 2022;10(7):650–660. doi:10.1016/S2213-2600(21)00537-3
   PubMed Web of Science ®Google Scholar
• Sverrild A, Hansen S, Hvidtfeldt M, et al. The effect of tezepelumab on airway hyperresponsiveness to mannitol in asthma (UPSTREAM). Eur Respir J. 2021;59(1):2101296. doi:10.1183/13993003.01296-2021
   PubMed Web of Science ®Google Scholar
• Diver S, Khalfaoui L, Emson C, et al. Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021;9(11):1299–1312. doi:10.1016/S2213-2600(21)00226-5
   PubMed Web of Science ®Google Scholar
• Emson C, Diver S, Chachi L, et al. CASCADE: a phase 2, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effect of tezepelumab on airway inflammation in patients with uncontrolled asthma. Respir Res. 2020;21(1):265. doi:10.1186/s12931-020-01513-x
   PubMed Web of Science ®Google Scholar
• Alpizar S, Megally A, Chen C, Raj A, Downie J, Colice G. Functionality and performance of an accessorized pre-filled syringe and an autoinjector for at-home administration of tezepelumab in patients with severe, uncontrolled asthma. J Asthma Allergy. 2021;14:381–392. doi:10.2147/JAA.S305114
   PubMed Web of Science ®Google Scholar
• Menzies-Gow A, Wechsler ME, Brightling CE, et al. Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study. Lancet Respir Med. 2023;11(5):425–483. doi:10.1016/S2213-2600(22)00492-1
   PubMed Web of Science ®Google Scholar
• Castro M, Kraft M, Ambrose CS, et al. Tezepelumab reduces patient-reported cough and phlegm production in patients with severe, uncontrolled asthma: results from the phase 3 NAVIGATOR study. Presented at: American Thoracic Society (ATS). Washington DC, USA; 2023.
   Google Scholar
• Sverrild A, Cerps S, Nieto-Fontarigo J, et al. Effects of tezepelumab on host epithelial tolerance to virus in patients with uncontrolled asthma. Presented at: European Respiratory Society (ERS). Virtual meeting; 2021.
   Google Scholar
• Oppenheimer J, Hoyte FCL, Phipatanakul W, Silver J, Howarth P, Lugogo NL. Allergic and eosinophilic asthma in the era of biomarkers and biologics: similarities, differences and misconceptions. Ann Allergy Asthma Immunol. 2022;129(2):169–180. doi:10.1016/j.anai.2022.02.021
   PubMed Web of Science ®Google Scholar
• Griffiths JM, Pham T-H, Wang E, et al. Tezepelumab reduces inflammatory biomarkers as early as week 2 and maintains reductions through week 52 in the phase 3 NAVIGATOR severe asthma trial. Presented at: American Academy of Allergy, Asthma and Immunology (AAAAI). Phoenix, AZ, USA; 2022.
   Google Scholar
• Corren J, Spahn JD, Ambrose CS, et al. Effect of tezepelumab on asthma inflammatory biomarker levels varies by baseline biomarker levels. Presented at: American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting. Louisville, KY, USA; 2022.
   Google Scholar
• Dweik RA, Boggs PB, Erzurum SC, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602–615. doi:10.1164/rccm.9120-11ST
   PubMed Web of Science ®Google Scholar
• Nordenmark L, Emson C, Hellqvist Å, et al. Tezepelumab reduced mucus plugs in patients with moderate-to-severe asthma. Presented at: European Respiratory Society (ERS). Barcelona, Spain; 2022.
   Google Scholar
• Nordenmark LH, Hellqvist Å, Emson C, et al. Tezepelumab and mucus plugs in patients with moderate-to-severe asthma. NEJM Evidence. 2023;2(10). doi:10.1056/EVIDoa2300135
   PubMedGoogle Scholar
• Corren J, Cook B, Ambrose CS, et al. Efficacy of tezepelumab in patients with severe, uncontrolled asthma: a pooled analysis of the phase 2b PATHWAY and phase 3 NAVIGATOR studies. Presented at: American Academy of Allergy, Asthma and Immunology (AAAAI) Annual Meeting. Phoenix, AZ, USA; 2022.
   Google Scholar
• Corren J, Menzies-Gow A, Chupp G, et al. Efficacy of tezepelumab in severe, uncontrolled asthma: pooled analysis of PATHWAY and NAVIGATOR studies. Am J Respir Crit Care Med. 2023;208(1):13–24. doi:10.1164/rccm.202210-2005OC
   PubMed Web of Science ®Google Scholar
• Kraft M, Corren J, Ambrose C, et al. Clinically meaningful improvements in St George’s Respiratory Questionnaire score with tezepelumab versus placebo in patients with severe, uncontrolled asthma: results from the phase 3 NAVIGATOR study. Presented at: American Thoracic Society (ATS). San Francisco, CA, USA; 2022.
   Google Scholar
• Jain JP, Ambrose CS, Cook B, Ponnarambil S, Martin N, Webb L. Efficacy of tezepelumab in patients with severe, uncontrolled asthma and high baseline blood eosinophil counts. Presented at: American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting. Louisville, KY, USA; 2022.
   Google Scholar
• Menzies-Gow ACJ, Corren J, Israel E, et al. Tezepelumab efficacy in patients with severe, uncontrolled asthma and comorbid nasal polyps in NAVIGATOR. Presented at: European Respiratory Society (ERS) International Congress. Virtual meeting; 2021.
   Google Scholar
• Jacobs JS, Hoyte FCL, Spahn JD, et al. Tezepelumab efficacy by SNOT-22 score in patients with severe, uncontrolled asthma and comorbid nasal polyps in NAVIGATOR. Presented at: American Academy of Allergy, Asthma and Immunology (AAAAI). San Antonio, TX, USA; 2023.
   Google Scholar
• Spahn JD, Jacobs JS, Hoyte FCL, et al. Tezepelumab efficacy by SNOT-22 domain scores in patients with severe, uncontrolled asthma and comorbid nasal polyps in the phase 3 NAVIGATOR study. Poster presentation presented at: American Thoracic Society (ATS). Washington DC, USA; 2023.
   Google Scholar
• Gauvreau GM, O’Byrne PM, Boulet LP, et al. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N Engl J Med. 2014;370(22):2102–2110. doi:10.1056/NEJMoa1402895
   PubMed Web of Science ®Google Scholar
• Caminati M, Llanos JP, Spahn J, et al. Changes in serum total IgE after cessation of tezepelumab after 2 years of treatment (DESTINATION). Presented at: European Respiratory Society (ERS) International Congress. Milan, Italy; 2023.
   Google Scholar
• Corren J, Larson D, Altman MC, et al. Effects of combination treatment with tezepelumab and allergen immunotherapy on nasal responses to allergen: a randomized controlled trial. J Allergy Clin Immunol. 2023;151(1):192–201. doi:10.1016/j.jaci.2022.08.029
   PubMed Web of Science ®Google Scholar
• Corren J, Ambrose CS, Griffiths JM, et al. Efficacy of tezepelumab in patients with evidence of severe allergic asthma: results from the phase 3 NAVIGATOR study. Clin Exp Allergy. 2023;53(4):417–428. doi:10.1111/cea.14256
   PubMed Web of Science ®Google Scholar
• Corren J, Ambrose CS, Sałapa K, et al. Efficacy of tezepelumab in patients with severe, uncontrolled asthma and perennial allergy. J Allergy Clin Immunol Pract. 2021;9(12):4334–4342.e6. doi:10.1016/j.jaip.2021.07.045
   PubMed Web of Science ®Google Scholar
• Corren J, Menzies-Gow A, Ambrose C, et al. Effect of tezepelumab on seasonal exacerbations in patients with severe, uncontrolled asthma grouped by blood eosinophil count. Presented at: European Respiratory Society (ERS). Barcelona, Spain; 2022.
   Google Scholar
• Corren J, Lindsley AW, Spahn J, et al. Tezepelumab reduces exacerbations across all seasons in patients with severe, uncontrolled asthma with seasonal allergy: results from the phase 3 NAVIGATOR study. Presented at: American Academy of Allergy, Asthma and Immunology (AAAAI). San Antonio, TX, USA; 2023.
   Google Scholar
• Corren J, Karpefors M, Hellqvist Å, Parnes JR, Colice G. Tezepelumab reduces exacerbations across all seasons in patients with severe, uncontrolled asthma: a post hoc analysis of the PATHWAY phase 2b study. J Asthma Allergy. 2021;14:1–11. doi:10.2147/JAA.S286036
   PubMed Web of Science ®Google Scholar
• Corren J, Welte T, Cook B, et al. Tezepelumab efficacy by number of sensitivities to perennial aeroallergens in NAVIGATOR. Presented at: American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting. New Orleans, LA, USA; 2021.
   Google Scholar
• Lindsley AW, Colice G, Spahn J, Martin N, Ambrose CS, Hoyte FCL. Efficacy of tezepelumab in patients with severe, uncontrolled asthma by specific perennial allergen immunoglobulin E thresholds. Poster presentation presented at: American Academy of Allergy, Asthma and Immunology (AAAAI). San Antonio, TX, USA; 2023.
   Google Scholar
• Menzies-Gow A, Corren J, Cook B, et al. Efficacy of tezepelumab in patients with severe, uncontrolled asthma, according to baseline blood eosinophil count and allergic status. Presented at: European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress; 2021.
   Google Scholar
• Denton E, Price DB, Tran TN, et al. Cluster analysis of inflammatory biomarker expression in the International Severe Asthma Registry. J Allergy Clin Immunol Pract. 2021;9(7):2680–2688 e7. doi:10.1016/j.jaip.2021.02.059
   PubMed Web of Science ®Google Scholar
• Chen M, Shepard K, Yang M, et al. Overlap of allergic, eosinophilic and type 2 inflammatory subtypes in moderate-to-severe asthma. Clin Exp Allergy. 2021;51(4):546–555. doi:10.1111/cea.13790
   PubMed Web of Science ®Google Scholar
• Kyriakopoulos C, Gogali A, Bartziokas K, Kostikas K. Identification and treatment of T2-low asthma in the era of biologics. ERJ Open Res. 2021;7(2):00309–2020. doi:10.1183/23120541.00309-2020
   PubMedGoogle Scholar
• Peters MC, Mekonnen ZK, Yuan S, Bhakta NR, Woodruff PG, Fahy JV. Measures of gene expression in sputum cells can identify TH2-high and TH2-low subtypes of asthma. J Allergy Clin Immunol. 2014;133(2):388–394. doi:10.1016/j.jaci.2013.07.036
   PubMed Web of Science ®Google Scholar
• Corren J, Brightling CE, Boulet LP, et al. Not just an anti-eosinophil drug: tezepelumab treatment for type 2 asthma and beyond. Eur Respir J. 2023;61(3):2202202. doi:10.1183/13993003.02202-2022
   PubMed Web of Science ®Google Scholar
• Peters MC, Ringel L, Dyjack N, et al. A transcriptomic method to determine airway immune dysfunction in T2-high and T2-low asthma. Am J Respir Crit Care Med. 2019;199(4):465–477. doi:10.1164/rccm.201807-1291OC
   PubMed Web of Science ®Google Scholar
• Cosío BG, Shafiek H, Iglesias A, et al. Validation of a pathological score for the assessment of bronchial biopsies in severe uncontrolled asthma: beyond blood eosinophils. Arch Bronconeumol. 2023;59(8):502–509. doi:10.1016/j.arbres.2023.05.014
   PubMed Web of Science ®Google Scholar
• Comeau MR, Ziegler SF. The influence of TSLP on the allergic response. Mucosal Immunol. 2010;3(2):138–147. doi:10.1038/mi.2009.134
   PubMed Web of Science ®Google Scholar
• Han NR, Oh HA, Nam SY, et al. TSLP induces mast cell development and aggravates allergic reactions through the activation of MDM2 and STAT6. J Invest Dermatol. 2014;134(10):2521–2530. doi:10.1038/jid.2014.198
   PubMed Web of Science ®Google Scholar
• Ambrose CS, Israel E, Bowen K, et al. Reply to Lipworth and Chan. Am J Respir Crit Care Med. 2023;208(2):212–213. doi:10.1164/rccm.202305-0843LE
   PubMedGoogle Scholar
• Lee H, Ryu J, Nam E, et al. Increased mortality in patients with corticosteroid-dependent asthma: a nationwide population-based study. Eur Respir J. 2019;54(5):1900804. doi:10.1183/13993003.00804-2019
   PubMed Web of Science ®Google Scholar
• Ambrose CS, Chipps BE, Moore WC, et al. The CHRONICLE study of US adults with subspecialist-treated severe asthma: objectives, design, and initial results. Pragmat Obs Res. 2020;11:77–90. doi:10.2147/POR.S251120
   PubMed Web of Science ®Google Scholar
• Wechsler ME, Menzies-Gow A, Brightling CE, et al. Oral corticosteroid-sparing effect of tezepelumab in adults with severe asthma: results from the DESTINATION study. Presented at: American Thoracic Society (ATS). Washington, DC, USA; 2023.
   Google Scholar
• Ando K, Fukuda Y, Tanaka A, Sagara H. 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. Cells. 2022;11(5):819. doi:10.3390/cells11050819
   PubMed Web of Science ®Google Scholar
• Nopsopon T, Lassiter G, Chen ML, et al. Comparative efficacy of tezepelumab to mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: a Bayesian network meta-analysis. J Allergy Clin Immunol. 2023;151(3):747–755. doi:10.1016/j.jaci.2022.11.021
   PubMed Web of Science ®Google Scholar
• Hanania NA, Alpan O, Hamilos DL, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med. 2011;154(9):573–582. doi:10.7326/0003-4819-154-9-201105030-00002
   PubMed Web of Science ®Google Scholar
• Korn S, Cook B, Simpson LJ, Llanos JP, Ambrose CS. Efficacy of biologics in severe, uncontrolled asthma stratified by blood eosinophil count: a systematic review. Adv Ther. 2023;40(7):2944–2964. doi:10.1007/s12325-023-02514-0
   PubMed Web of Science ®Google Scholar