Tezspire

The efficacy of Tezspire was evaluated in two randomized, double-blind, parallel group, placebo-controlled clinical trials (PATHWAY [Clinicaltrials.gov Identifier: NCT02054130] and NAVIGATOR [Clinicaltrials.gov Identifier: NCT03347279]) of 52 weeks duration. The two trials enrolled a total of 1609 patients 12 years of age and older with severe asthma. 

PATHWAY was a 52-week dose-ranging exacerbation trial that enrolled 550 adult patients with severe asthma who received treatment with tezepelumab-ekko 70 mg subcutaneously every 4 weeks, Tezspire 210 mg subcutaneously every 4 weeks, tezepelumab-ekko 280 mg subcutaneously every 2 weeks, or placebo subcutaneously. 

NAVIGATOR was a 52-week exacerbation trial that enrolled 1061 patients (adult and pediatric patients 12 years of age and older) with severe asthma who received treatment with Tezspire 210 mg subcutaneously every 4 weeks or placebo subcutaneously every 4 weeks. 

Exacerbations 

The primary endpoint for PATHWAY and NAVIGATOR was the rate of clinically significant asthma exacerbations measured over 52 weeks.

• In both studies, patients receiving Tezspire had significant reductions in the annualized rate of asthma exacerbations vs placebo (NAVIGATOR: 0.93 vs 2.10; rate ratio, 0.44 [95% CI, 0.37-0.53]; PATHWAY: 0.20 vs 0.72; rate ratio, 0.29 [95% CI, 0.16-0.51]).
• There were also fewer exacerbations requiring emergency room visits and/or hospitalization in patients treated with Tezspire compared with placebo (NAVIGATOR: 0.06 vs 0.28; rate ratio, 0.21 [95% CI, 0.12-0.37]; PATHWAY: 0.03 vs 0.18; rate ratio, 0.15 [95%, 0.04-0.58]).
• Exacerbations requiring hospitalization were also reduced in the Tezspire group vs placebo (NAVIGATOR: 0.03 vs 0.19; rate ratio, 0.15 [95% CI, 0.07-0.22]; PATHWAY: 0.02 vs 0.14; rate ratio, 0.14 [95% CI, 0.03-0.71]).

The time to first exacerbation was longer for the patients receiving Tezspire compared with placebo in NAVIGATOR (see full labeling). Similar findings were seen in PATHWAY.

Lung Function 

Change from baseline in FEV₁ was assessed as a secondary endpoint in PATHWAY and NAVIGATOR. Compared with placebo, Tezspire provided clinically meaningful improvements in the mean change from baseline in FEV₁ in both trials.

Over 52 weeks, the mean change from baseline in FEV₁ (difference from Tezspire and placebo) was:

• 0.13 L; (95% CI, 0.08-0.18) in NAVIGATOR,
• 0.13 L; (95% CI, 0.03-0.23) in PATHWAY.

In NAVIGATOR, improvement in FEV₁ was seen as early as 2 weeks after initiation of treatment and was sustained through week 52.

Patient Reported Outcomes 

Changes from baseline in Asthma Control Questionnaire 6 (ACQ-6) and Standardized Asthma Quality of Life Questionnaire for ages 12 and older [AQLQ(S)+12] were also assessed as secondary endpoints in PATHWAY and NAVIGATOR. 

In both trials, more patients treated with Tezspire compared to placebo had a clinically meaningful improvement in ACQ-6 and AQLQ(S)+12. The responder rate for both measures was defined as improvement in score of 0.5 or more at the end of trial. 

• In NAVIGATOR, the ACQ-6 responder rate for Tezspire was 86% vs 77% for placebo (OR=1.99; 95% CI, 1.43-2.76) and the AQLQ(S)+12 responder rate for Tezspire was 78% vs 72% for placebo (OR=1.36; 95% CI, 1.02-1.82).
• Similar findings were seen in PATHWAY.