NAVIGATOR: Smooth sailing across the board for tezepelumab in severe asthma

The specific TSLP* inhibitor tezepelumab significantly reduces exacerbation rates across a broad spectrum of patients with severe, uncontrolled asthma, regardless of the status of key inflammatory biomarkers, according to the NAVIGATOR study presented at ATS 2021.

Not only did tezepelumab lead to clinical benefits in terms of reduced asthma exacerbations and improved lung function, asthma control and symptoms, it also lessened the burden severe asthma place on healthcare resources — by cutting the need for hospitalizations or ED** visits due to severe asthma.

“Even with biologic treatment, about 60 percent of US patients with severe asthma have suboptimally controlled disease,” pointed out presenting author Professor Michael Wechsler from National Jewish Health in Denver, Colorado, US. “There is a need for alternative treatments for severe asthma that treat a wider spectrum of inflammation.”

Tezepelumab is a first-in-class anti-TSLP monoclonal antibody that selectively blocks TSLP, which is involved in a wide spectrum of inflammatory processes leading to asthma, regardless of whether it is T2 or non-T2 inflammation. 

“By blocking TSLP, tezepelumab reduces the initiation and persistence of airway inflammation by interfering with multiple downstream inflammatory pathways,” explained Wechsler.

Doing away with biomarkers?

At 1 year, tezepelumab more than halved the annual rate of asthma exacerbations (0.93 vs 2.10; p<0.001) — translating to a significant reduction by 56 percent compared with placebo. [ATS 2021, session B007; N Engl J Med 2021;384:1800-1809]

When stratified by baseline blood eosinophil counts (BEC), the exacerbation rate was significant lower by 41 percent with tezepelumab vs placebo among patients with BEC of <300 cells/µL (1.02 vs 1.73; p<0.001).

This reduction persisted across a broad range of inflammatory profiles, regardless of baseline BEC, FeNO*** levels, and IgE status. 

“Tezepelumab is the first and only asthma biologic to consistently demonstrate in randomized trials clinically meaningful exacerbation reductions irrespective of key biomarkers, including BEC, allergic status and FeNO,” the investigators said.

“Tezepelumab offers new therapeutic opportunities for patients who are currently ineligible for biologic treatments,” said study co-author Professor Arnaud Bourdin from the University of Montpellier in Montpellier, France. “It may also challenge the current mandatory step of biomarker assessment before initiating a biologic.”

Further benefits

Tezepelumab also led to improvement in lung function, as indicated by change in pre-bronchodilator FEV₁ over 52 weeks — both in the overall population as well as in stratified subgroups regardless of baseline BEC.

“This improvement was seen early on in the overall population and was sustained throughout the study,” reported Wechsler.

Other secondary outcomes such as asthma control, asthma symptoms, and quality of life were also better in the tezepelumab than the placebo groups over 52 weeks.

In addition, exacerbations requiring hospitalizations or ED visits were significantly lower by 79 percent with tezepelumab vs placebo (annualized rate, 0.06 vs 0.28; p<0.001).

“These results show that tezepelumab has the potential not only to treat a broad population of severe asthma patients but also to reduce the burden severe asthma places on healthcare systems,” said Wechsler and co-authors. “Once on the market, this therapy presents the real possibility that severe asthma patients will no longer have to be hospitalized.”

*TSLP: Thymic stromal lymphopoietin
**ED: Emergency department
***FeNO: fractional exhaled nitric oxide