American Thoracic Society International Conference

American Thoracic Society International Conference

Source:

Corren J, et al. B101 – New Biological Treatments for Asthma. Presented at: American Thoracic Society Virtual; Aug. 5-10, 2020 (virtual meeting).

Disclosures: The PATHWAY study was co-sponsored by AstraZeneca and Amgen.
August 17, 2020
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Tezepelumab reduces exacerbations in broad population of patients with severe asthma

Source:

Corren J, et al. B101 – New Biological Treatments for Asthma. Presented at: American Thoracic Society Virtual; Aug. 5-10, 2020 (virtual meeting).

Disclosures: The PATHWAY study was co-sponsored by AstraZeneca and Amgen.
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New analyses of the phase 2b PATHWAY study demonstrate that treatment with tezepelumab reduced asthma exacerbations and inflammation in a broad population of patients with severe, uncontrolled asthma.

Healio previously reported results from the randomized, double-blind, placebo-controlled, multicenter, phase 2 PATHWAY study, which enrolled adults with severe, uncontrolled asthma, despite treatment with long-acting beta agonist therapy and medium to high doses of inhaled glucocorticoids. Patients were randomly assigned 70 mg tezepelumab (AstraZeneca) every 4 weeks (n = 138), 210 mg tezepelumab every 4 weeks (n = 137), 280 mg tezepelumab every 2 weeks (n = 137) or placebo every 2 weeks (n = 138). Results from the main trial showed tezepelumab reduced clinically significant asthma exacerbations compared with placebo, regardless of blood eosinophil counts.

Asthma medications
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In a new post hoc analysis of tezepelumab, reported as an e-poster at the American Thoracic Society Virtual meeting, researchers evaluated annualized asthma exacerbation rates according to baseline levels of serum interleukin (IL)-5 and IL-13 and assessed the association with conventional type 2 biomarkers.

Baseline blood eosinophil counts, fractional exhaled nitric oxide (FeNO) and total serum immunoglobulin E were higher among patients with high IL-5 and IL-3. In addition, patients with high IL-5 and IL-3 were more likely to use maintenance oral corticosteroids and have nasal polyps compared with those with low IL-5 and IL-3.

Over 52 weeks, the annualized asthma exacerbation rate in the placebo group was higher in patients with high IL-5 and IL-13 compared with patients with lower IL-5 and IL-13 (1.09 vs. 0.92). The annualized asthma exacerbation rates in the group assigned tezepelumab 210 mg was reduced by 68% (95% CI, 27-86) in patients with high IL-5 and IL-3 and reduced by 85% (95% CI, 51-95) in patients with low IL-5 and IL-3, according to the results. The researchers observed similar reductions in a pooled tezepelumab dose group, with a 74% (95% CI, 47-87) reduction in patients with high serum levels and an 81% (95% CI, 58-91) reduction in patients with low serum levels, compared with placebo, according to the poster.

Another post hoc analysis evaluated the effect of tezepelumab in patients with severe, uncontrolled asthma, both with and without self-reported nasal polyps. Overall, 15.2% of patients in the PATHWAY study had nasal polyps.

Baseline blood eosinophil counts were higher in patients with nasal polyps compared with those without nasal polyps (537.7 cells/L vs. 342.3 cells/L). About 75% of patients with nasal polyps had eosinophil counts of at least 300 cells/L compared with 44.8% of patients without nasal polyps. At baseline, a higher proportion of patients with nasal polyps were taking high-dose inhaled glucocorticoids and maintenance oral corticosteroids, had elevated FeNO levels, had three or more exacerbations in the previous year, and had elevated serum levels of IL-5 and IL-3 compared with patients without nasal polyps.

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Patients with nasal polyps who were assigned placebo had a higher annualized asthma exacerbation rate (1.08; 95% CI, 0.65-1.68) compared with patients without nasal polyps (0.68; 95% CI, 0.54-0.85). Compared with placebo, tezepelumab reduced the annualized asthma exacerbation rate by 75% (95% CI, 15-93) in patients with nasal polyps and by 73% (95% CI, 47-86) in patients without nasal polyps. Additionally, treatment with tezepelumab 210 mg every 4 weeks decreased blood eosinophil counts and levels of FeNO and serum IL-5 and IL-3 compared with placebo, irrespective of the presence of nasal polyps.

In a third post hoc analysis of the PATHWAY trial, researchers assessed changes in blood eosinophil counts and FeNO levels from baseline to 52 weeks and then 14 to 16 weeks after the final tezepelumab dose.

Researchers reported in the poster that suppression of type 2 inflammation, which was evaluated as the proportion of patients within various blood eosinophil and FeNO subgroups, persisted for 14 to 16 weeks after cessation of treatment with tezepelumab.

A fourth post hoc analysis demonstrated seasonal variability in exacerbations in patients with severe, uncontrolled asthma.

From 2014 to 2017, the annualized asthma exacerbation rate was highest in the winter, followed by fall and summer, and lowest in the spring, across all treatment groups, according to the results. In patients assigned tezepelumab 210 mg, the annualized asthma exacerbation rate was reduced by 64% during winter, 82% during spring, 82% during summer, 67% during fall compared with placebo. In a pooled tezepelumab group, the annualized asthma exacerbation rate was reduced by 63% during winter, 70% during spring, 77% during summer and 63% during fall compared with placebo.

In other results, the proportion of patients who experienced one or more exacerbation was lower during all seasons and the proportion of patients with exacerbations per day were reduced in those assigned tezepelumab 210 mg and in the pooled tezepelumab group compared with placebo.

These analyses support the benefit of tezepelumab reducing asthma exacerbation rates in a broad range of patients with severe, uncontrolled asthma, the researchers concluded.

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin from interacting with the receptor complex.

Tezepelumab was granted breakthrough therapy designation by the FDA in 2018 to treat patients with severe asthma without an eosinophilic phenotype who are receiving inhaled corticosteroids and LABAs with or without additional asthma controllers.

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