Tezepelumab Benefits Uncontrolled Asthma in Subgroup Analyses of IL-5, IL-13 Levels, CRSwNP Status

Tezepelumab yielded greater reductions in asthma exacerbations in patients with severe, uncontrolled asthma with elevated serum IL-5 and IL-13 levels than those without elevated levels compared to placebo.1

These findings, from the phase 3 NAVIGATOR study (NCT03347279), will be presented at the 2025 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress, February 28-March 3, in San Diego, California, by Flavia Hoyte, MD, Professor and Director, Allergy & Clinical Immunology Fellowship, Department of Medicine, Division of Allergy & Clinical Immunology, National Jewish Health.

“Interleukin (IL)-5 and IL-13 are common drivers of inflammation in severe asthma. In the phase 3 NAVIGATOR study, tezepelumab reduced serum IL-5 and IL-13 levels and the annualized asthma exacerbation rate (AAER) in patients with severe, uncontrolled asthma,” Hoyte and colleagues wrote.1

NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study that enrolled 1059 patients (tezepelumab, n = 528; placebo, n = 531) between the ages of 12-80 years with severe, uncontrolled asthma to be randomized to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Investigators estimated AAER for tezepelumab and placebo recipients grouped by ≥ or < median baseline serum IL-5 and IL-13 levels: IL-5-high/IL-13-high, IL-5-high/IL-13-low, IL-5-low/IL-13-high, IL-5-low/IL-13-low.

Participants in the study had median baseline IL-5 levels of 0.86 pg/mL and IL-13 levels of 0.05 pg/mL. Most patients were IL-5-high/IL-13-high (tezepelumab, n = 206; placebo, n = 197) or IL-5-low/IL-13-low (tezepelumab, n = 204; placebo, n = 192). Fewer patients were IL-5-high/IL-13-low (tezepelumab, n = 51; placebo, n = 57) or IL-5-low/IL-13-high (tezepelumab, n = 52; placebo, n = 60). Hoyte and colleagues found that the placebo group had higher AAER over 52 weeks in IL-5-high/IL-13-high patients than in IL-5-low/IL-13-low patients (2.54 [95% CI, 2.07-3.12] vs 1.94 [95% CI, 1.57-2.40], respectively). Participants with IL-5-high/IL-13-high receiving tezepelumab had greater absolute and relative AAER reductions versus placebo (difference: −1.77 [95% CI, −2.31 to −1.23]; rate ratio: 0.30 [95% CI, 0.22-0.41]) than those who had IL-5-low/IL-13-low levels (difference: −0.77 [95% CI, −1.24 to −0.29]; rate ratio: 0.61 [95% CI, 0.45-0.82]).1

Other subgroup analyses from NAVIGATOR being presented at the AAAAI/WAO Joint Congress found that tezepelumab improved fatigue and activity levels in patients with severe, uncontrolled asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) compared with placebo.2,3

Of NAVIGATOR’s participants, 165 had a history of CRSwNP (tezepelumab, n=90; placebo, n=75) and completed the SNOT-22 and completed the AQLQ(S)+12 questionnaires. Investigators found that at week 28, the least-squares mean (LSM) change from baseline for the SNOT-22 Fatigue item was −1.02 in the tezepelumab group compared with −0.32 in the placebo group (LSM difference, −0.70 [95% CI, −1.13 to −0.28]). At week 52, the LSM change from baseline was −1.05 in the tezepelumab group compared with –0.48 in the placebo group (LSM difference, − 0.57 [95% CI: −1.00 to −0.15]). At week 52, more participants who received tezepelumab versus placebo, with non-missing baseline and week 52 data, were responders for the SNOT-22 Fatigue item (39% vs 31% respectively; odds ratio [OR], 2.58 [95% CI, 0.89-7.46]).2

In looking at activity levels, investigators found that more patients who received tezepelumab were responders than those who received placebo for strenuous activities (52% vs 24%), moderate activities (55% vs 33%), work/school-related activities (49% vs 31%) and overall range of activities (49% vs 29%), with ORs ranging from 3.00 (95% CI, 1.29–6.94) for work/school-related activities to 5.19 (95% CI, 2.14–12.54) for strenuous activities. Notably, the investigators found that participants with CRSwNP treated with tezepelumab versus placebo had higher response rates than in the overall study population, with the highest OR of 1.47 (95% CI, 1.11–1.97) for strenuous activities.3

REFERENCES

1. Hoyte F, Mathur S, Carr T, et al. Efficacy Of Tezepelumab In Patients With Severe, Uncontrolled Asthma Grouped By Median Baseline Serum IL-5 And IL-13 Levels: Results From The Phase 3 NAVIGATOR Study. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3. Abstract 935

2. Jacobs J, Hoyte F, Han J, et al. Effect Of Tezepelumab On Fatigue In Patients With Severe, Uncontrolled Asthma And Chronic Rhinosinusitis With Nasal Polyps In The Phase 3 NAVIGATOR Study. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3. Abstract 233

3. Peters A, Han J, Lee S, et al. Effect Of Tezepelumab On Activity Levels In Patients With Severe, Uncontrolled Asthma And Chronic Rhinosinusitis With Nasal Polyps In The Phase 3 NAVIGATOR Study. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3. Abstract 230