PHOENIX — Patients with severe, uncontrolled asthma experienced greater relief throughout the year when treated with the biologic tezepelumab (Tezspire) versus placebo, according to findings from the phase III NAVIGATOR study.
Over 52 weeks, tezepelumab significantly reduced the annualized asthma exacerbation rate by 56% in the overall study population (P<0.001), and by 41% in those with baseline blood eosinophil counts below 300 cells/µL (P<0.001), reported Andrew Lindsley, MD, PhD, medical director at Amgen in Thousand Oaks, California, during the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting.
When stratified by season, the annualized asthma exacerbation rate was consistently reduced with tezepelumab:
- Winter: 2.62 with placebo versus 0.96 with tezepelumab, for a reduction of 63% (95% CI 52-72)
- Spring: 1.71 versus 0.92, for a reduction of 46% (95% CI 26-61)
- Summer: 1.93 versus 0.73, for a reduction of 62% (95% CI 48-73)
- Fall: 2.28 versus 1.05, for a reduction of 54% (95% CI 41-64)
Tezepelumab inhibits thymic stromal lymphopoietin, which is a key component of airway inflammation and is thought to be released in response to airborne triggers of asthma, such as pollen and viruses. In a prior analysis of NAVIGATOR, as well as the phase IIb PATHWAY study, tezepelumab was shown to reduce exacerbations when compared with placebo.
In another study presented at AAAAI, treatment with dupilumab (Dupixent) was shown to have similar results. In an analysis of the 52-week QUEST study, which established the effectiveness of dupilumab as an add-on treatment for asthma, and the 96-week TRAVERSE open-label extension trial, researchers found that asthma exacerbations were reduced to below 7% all year long — and most of the time it was less than 5%.
In NAVIGATOR, the researchers performed the seasonal studies because variations in the frequency of asthma exacerbations can occur due to the presence of different triggers.
“We know that allergies are seasonal, but depend on the trigger for asthma — early spring is the tree pollen season, late spring is grass pollen, in the fall it is ragweed, and then in winter the viruses or dust mites or mold,” Roxana Siles, MD, co-director of the asthma center at the Cleveland Clinic, told MedPage Today.
“There has been a question of how much these biologics such as tezepelumab and dupilumab were affected by the seasons, and what we found out in this session is that they are really effective in all seasons,” she said. “We also see that these drugs work on all types of asthma triggers, whether the person has allergic asthma or non-allergic asthma. I found it fascinating that both these drugs work throughout the year.”
The study also showed that tezepelumab decreased the proportion of patients with at least one exacerbation during all seasons, from 33.4% to 18.3% in the winter, 23.7% to 15.7% in the spring, 26.9% to 13.2% in the summer, and 33.4% to 20.6% in the fall.
The mean number of days with an exacerbation per patient was also reduced:
- 4.9 to 1.9 days in the winter
- 3.6 to 1.7 days in the spring
- 3.6 to 1.5 days in the summer
- 4.3 to 2.1 days in the fall
The international, randomized, double-blind, placebo-controlled NAVIGATOR study included 1,059 patients, 528 randomized to tezepelumab 210 mg subcutaneously every 4 weeks for 52 weeks and 531 randomized to placebo injections. In both groups, mean age was about 49, and approximately 63% were women. Baseline blood eosinophil counts were similar between groups. Data from patients in the Southern Hemisphere were transformed to align with Northern Hemisphere seasons.
The NAVIGATOR trial was supported by Amgen, AstraZeneca, and Biopharmaceutical Research & Development.
Lindsley is an employee of Amgen.
Siles disclosed a relationship with DynaMed.