AstraZeneca and Amgen presented full results from the Phase III NAVIGATOR study on Friday, with findings showing that the addition of tezepelumab to standard care treatment reduced annualised asthma exacerbation rates (AAERs) by 56% in patients with severe, uncontrolled asthma, compared to placebo, with benefits seen regardless of baseline eosinophil count. The results, presented at the American Academy of Asthma Allergy & Immunology (AAAAI) annual meeting, come after the companies announced last November that the TSLP targeting monoclonal antibody had achieved the trial's primary endpoint.
Mene Pangalos, who heads BioPharmaceuticals R&D at AstraZeneca, said the findings show tezepelumab to be the first asthma biologic that has demonstrated "clinically meaningful exacerbation reductions, irrespective of blood eosinophil counts, allergy status and fractional exhaled nitric oxide (FeNO)." He also suggested that NAVIGATOR adds to a "strong body of evidence showing the benefit of targeting the top of the inflammatory cascade with tezepelumab."
The trial randomised 1059 adults and adolescents ranging from 12 to 80 years of age with severe uncontrolled asthma to receive subcutaneous injections of tezepelumab or placebo over a period of 52 weeks. This was on top of standard treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication, with or without oral corticosteroids (OCS). The trial enroled approximately equal proportions of patients with high and low blood eosinophil counts.
Other results presented at the AAAAI meeting showed that tezepelumab reduced the AAER by 70% in patients whose baseline blood eosinophil counts were ≥300 cells per µL. For those with blood eosinophil counts of <300 cells per µL and <150 cells/µL, AAER was reduced by 41% and 39%, respectively. Principal investigator Andrew Menzies-Gow remarked that tezepelumab could potentially "transform treatment for a broad population of patients with severe asthma regardless of their type of inflammation."
Meanwhile, the companies reported that the drug also demonstrated significant improvements in every key secondary endpoint compared to placebo, including lung function measurements and asthma control, while also lowering the risk of hospitalisations or emergency visits by 79%.
The most common side effects included nasopharyngitis, upper respiratory tract infection and headache, with rates of serious adverse events being 8.7% for tezepelumab and 13.2% for placebo, although there were no clinically meaningful differences in safety results between the two groups. Researchers noted there were no reports of anaphylactic reactions or cases of Guillain–Barré syndrome related to the treatment.
"Alongside Fasenra (benralizumab), we think that having two really strong complimentary, robust biologics in this space will actually expand use in eligible patients," commented Richard Marshall, global head of AstraZeneca's respiratory and immunology unit, adding that the NAVIGATOR data will form part of regulatory submissions expected in the first half of 2021. The company reported sales of $283 million for Fasenra in the fourth quarter of 2020. The IL-5 antagonist is indicated as an add-on maintenance treatment for patients aged 12 and up with severe asthma with an eosinophilic phenotype.
Meanwhile, Sanofi and Regeneron Pharmaceuticals' Dupixent (dupilumab), a dual inhibitor of IL-4 and IL-13 signaling, is approved as add-on maintenance for moderate-to-severe asthma patients 12 and older with an eosinophilic phenotype or with OCS-dependent asthma. That drug generated €982 million ($1.5 billion) in the fourth quarter. In December, AstraZeneca and Amgen said tezepelumab had missed the primary endpoint of the Phase III SOURCE trial, failing to significantly reduce the daily amount of OCS needed by certain patients with severe asthma.
For related analysis, see ViewPoints: New data suggest Amgen, AstraZeneca's tezepelumab has done enough. See also Physician Views Results: Compelling exacerbation data now key for Amgen, AstraZeneca’s tezepelumab.
To read more Top Story articles, click here.