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TEZSPIRE^® (tezepelumab): study designs

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The phase IIb PATHWAY study examined the efficacy and safety of three doses of tezepelumab in adults with uncontrolled asthma¹

pathway-desktop

Adapted from Corren J, et al. NEJM. 2017.¹

Patient population: Non-smokers, 18–75 years, ACQ ≥1.5,medium- or high-dose ICS + LABA for ≥6 months ± other controllers, ± OCS, ≥2 exacerbations requiring SCS or 1 requiring hospitalisation in past year¹
Patients stratified by location (Japan or ROW), bEOS count (≥250 or <250 cells/μL), and dose level of inhaled glucocorticoids (medium or high)
Primary endpoint: AAER over 52 weeks¹
Key secondary endpoints: Change from baseline in:¹
- Pre-BD and post-BD FEV¹
- ACQ-6
- AQLQ(S)+12
- Asthma symptom score
Safety outcome: Adverse event incidence¹

AAER=annualised asthma exacerbation rate; ACQ-6=asthma control questionnaire-6 items; AQLQ(S)+12=standardised asthma quality of life questionnaire for 12 years and older; bEOS=blood eosinophils; BD=bronchodilator; FEV1=forced expiratory volume in the first second; ICS=inhaled corticosteroids; LABA=long-acting beta agonist; OCS=oral corticosteroids; Q2W=every 2 weeks; Q4W=every 4 weeks; R=randomisation; SC=subcutaneous; SCS=systemic corticosteroid.

NAVIGATOR phase III exacerbation study in adults and adolescents with severe, uncontrolled asthma^2,3

navigator

Adapted from Menzies-Gow A, et al. NEJM. 2021 and Menzies-Gow A et al Respir Res. 2020.^2,3

Patient population: Non-smokers, 12–80 years, ACQ ≥1.5,medium- or high-dose ICS + LABA for ≥12 months, ± OCS, and + ≥1 additional controller medication for ≥3 months, ≥2 exacerbations requiring SCS or 1 requiring hospitalisation in past year³
7.7% of subjects were adolescents (≥12 - <18 years, n=82)²
Exclusion criteria: any pulmonary disease other than asthma, infection requiring antibiotic or antiviral treatment in 2 weeks prior, helminth/parasitic infection in 6 months prior, history of cancer, HIV or hepatitis B or C , current smokers or those with a history of ≥10 pack-years, history of anaphylaxis after biologic therapy, pregnant, breastfeeding or lactating²
Primary endpoint:
- AAER over 52 weeks; all patients
- AAER over 52 weeks; Patients with baseline EOS <300 cells/µL
Key secondary endpoints: Change from baseline in: Pre-BD FEV1, ACQ-6 score, AQLQ(S)+12 score and ASD
Additional secondary endpoints:
- AAER associated with an ED visit or hospitalisation and hospitalisation only
- Change from baseline in FeNO, serum total IgE, bEOS
Safety outcome: Adverse event incidence³

AAER=annualised asthma exacerbation rate; ACQ-6=asthma control questionnaire-6 items; ASD=asthma symptom diary; AQLQ=Asthma Quality of Life Questionnaire; BD=bronchodilator; bEOS=blood eosinophils; ED=emergency department; EOS=eosinophils; FEV1=forced expiratory volume in the first second; FeNO=fractional exhaled nitric oxide; HIV=human immunovirus; IgE=immunoglobulin E; ICS=inhaled corticosteroids; LABA=long-acting beta agonist; LTRA=leukotriene receptor antagonist; OCS=oral corticosteroids; Q4W=every 4 weeks; R=randomisation; SC=subcutaneous;SCS=systemic corticosteroid.

Phase II CASCADE: mechanistic study observations^4-6

hospitalisation_panel_image

Figure adapted from Emson C, et al. Respir Resp. 2020, Diver S, et al. Lancet Respir Med. 2021 and Diver S, et al. Poster: ATS. International Conference. 2021.^4-6

Patient population: Medium to severe asthma, non-smokers, 18-75 years, ACQ ≥1.5, medium- or high-dose ICS for ≥12 months, and + ≥1 additional controller medication +/- maintenance OCS for ≥3 month⁵
Primary endpoint: Change from baseline to Week 28 in airway submucosal inflammatory cells (eosinophils, neutrophils, T cells and mast cells) from bronchoscopic biopsies⁴
Key secondary endpoints: Assessing airway remodeling, from change from baseline in reticular basement membrane (RBM) thickness and epithelial integrity (proportions of damaged, denuded and intact epithelium)⁴
Selected exploratory endpoint: Change from baseline to end of treatment in airway hyperresponsiveness to mannitol⁴
Limitations: Patients were recruited to this trial mainly on the basis of treatment requirements and lung function measures, which did not translate into the expected baseline histological features. Because bronchoscopies for research purposes were not permitted during COVID-19 pandemic in countries where the study was conducted, for participants who could not visit the study site at Week 28 owing to the COVID-19 pandemic, treatment was extended to up to 52 weeks until they were able to visit the study site^4,6
Safety outcome: Adverse event incidence⁴
The reduction in airway submucosal eosinophils with tezepelumab in this study was observed despite baseline submucosal eosinophil counts being lower than expected for patients with moderate-to-severe asthma⁴

TEZSPIRE (tezepelumab) is indicated as an add-on maintenance treatment in adults and adolescents 12 years and older with severe asthma who are inadequately controlled despite high dose inhaled corticosteroids plus another medicinal product for maintenance treatment⁷

ACQ=asthma control questionnaire; EOT=end of treatment; ICS=inhaled corticosteroid; LABA=long-acting beta agonist; LAMA=long-acting muscarinic antagonist; LTRA=leukotriene receptor antagonist; OCS=oral corticosteroids; Q4W=every 4 weeks; R=randomisation; SC=subcutaneous

Corren J, Parnes JR, Wang L, et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377(10):936-946.
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.
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.
Diver S, Khalfaoui L, Emson C, et al. CASCADE study investigators. 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.
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. 2020,21:265.
Diver S et al. Effect of tezepelumab on airway inflammatory cells, remodeling and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma: a randomized, double-blind, placebo-controlled trial (CASCADE) Poster presented at: ATS International Conference; May 14-19, 2021.
Tezspire (tezepelumab). Summary of Product Characteristics. 2022. Available at: https://www.medicines.org.uk/emc/product/14064/smpc (last accessed: November 2024).

GB-56754 | November 2024

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TEZSPIRE® (tezepelumab): study designs

The phase IIb PATHWAY study examined the efficacy and safety of three doses of tezepelumab in adults with uncontrolled asthma1

NAVIGATOR phase III exacerbation study in adults and adolescents with severe, uncontrolled asthma2,3

Phase II CASCADE: mechanistic study observations4-6

Abbreviations and References

TEZSPIRE^® (tezepelumab): study designs

The phase IIb PATHWAY study examined the efficacy and safety of three doses of tezepelumab in adults with uncontrolled asthma¹

NAVIGATOR phase III exacerbation study in adults and adolescents with severe, uncontrolled asthma^2,3

Phase II CASCADE: mechanistic study observations^4-6