Response analysis further establishes tezepelumab benefit in severe uncontrolled asthma

Adolescents and adults with severe uncontrolled asthma while on inhaled corticosteroids (ICS) had greater responses to the human monoclonal antibody tezepelumab than placebo, according to prespecified exploratory results of the phase III NAVIGATOR trial.

“Across all four response criteria [assessed], more tezepelumab-treated patients with severe, uncontrolled asthma achieved clinical responses compared with placebo recipients,” said study author Associate Professor Njira Lugogo from the University of Michigan, Ann Arbor, Michigan, US, who presented the findings at ATS 2022.

The multicentre, double-blind trial involved 1,059 non-smoking patients aged 12–80 years with severe uncontrolled asthma while on medium-to-high dose ICS* for ≥12 months and ≥1 additional asthma medication with/without oral corticosteroids (OCS) for ≥3 months. Patients needed to have experienced ≥2 exacerbations in the prior 12 months warranting hospitalization, emergency department visit resulting in ≥3 consecutive days of systemic corticosteroid therapy, or systemic corticosteroid use for ≥3 consecutive days.

They were randomized 1:1 to receive subcutaneous tezepelumab (210 mg) or placebo Q4W for 52 weeks in addition to standard of care. This exploratory analysis assesses clinical response among those who completed the on-treatment period and had no missing data on any response criteria at week 52 (n=431 and 420 in the tezepelumab and placebo groups, respectively).

More patients in the tezepelumab than placebo group experienced a ≥50-percent reduction in exacerbations on-treatment at week 52 compared with the previous year (85 percent vs 68 percent; odds ratio [OR], 2.73, 95 percent confidence interval [CI], 1.98–3.77). [ATS 2022, Session B93 - Breakthroughs in Pediatric and Adult Asthma Clinical Trials]

At week 52, a greater proportion of patients in the tezepelumab than placebo group experienced a ≥0.5 improvement from baseline in Asthma Control Questionnaire (ACQ)-6 total score (87 percent vs 77 percent; OR, 1.99, 95 percent CI, 1.38–2.87) and a ≥100 mL or ≥5-percent improvement from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV₁; 60 percent vs 50 percent; OR, 1.52, 95 percent CI, 1.15–2.01).

More patients in the tezepelumab than placebo group had a Clinical Global Impression of Change (CGI-C) score defined as minimally, much, or very much improved (82 percent vs 68 percent; OR, 2.25, 95 percent CI, 1.61–3.14).

Overall, complete response while on treatment, which analysed patients who had responses to all four criteria, occurred in more patients in the tezepelumab than placebo group (46 percent vs 24 percent; OR, 2.83, 95 percent CI, 2.10–3.82).

More complete responders in the tezepelumab than placebo group were on maintenance OCS at baseline, experienced >2 exacerbations in the past 12 months, and had higher baseline fractional exhaled nitric oxide levels and blood eosinophil counts.

“Despite maximal standard-of-care therapy, patients with severe uncontrolled asthma experience exacerbations and poorly controlled symptoms, which may result in reduced health-related quality of life,” said Lugogo.

Prior results of the NAVIGATOR trial showed a significant 56-percent reduction in exacerbations with tezepelumab vs placebo (annualized rate 0.93 vs 2.10; rate ratio, 0.44), as well as significant improvements in pre-bronchodilator FEV₁, ACQ-6 scores, and other quality-of-life assessments at 52 weeks. [N Engl J Med 2021;384:1800-1809]

“[In the present analysis,] in total, 40–46 percent of patients in the tezepelumab group experienced a complete on-treatment response across all four response criteria, at 2.8-fold higher odds than with placebo.”

“These data further support the efficacy of tezepelumab in a broad population of patients with severe, uncontrolled asthma,” Lugogo concluded.

*fluticasone propionate ≥500 µg/day or equivalent