AstraZeneca has reported positive high-level results from the phase 3 MIRANDA trial of tozorakimab, showing a statistically significant reduction in moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease (COPD).
The trial attained its primary endpoint in a population of former smokers and the overall population, which included both former and current smokers. Benefits were observed across all blood eosinophil counts and levels of lung function severity.
In the MIRANDA trial, 1,454 patients with symptomatic COPD and a history of exacerbations received tozorakimab 300mg or a placebo every two weeks, in addition to inhaled standard-of-care therapy, over 52 weeks. All participants had been receiving inhaled maintenance therapy for at least three months prior to enrolment but continued to experience moderate-to-severe exacerbations.
The findings follow previously reported positive results from the phase 3 OBERON and TITANIA trials, which evaluated a four-week dosing regimen of tozorakimab in a similar patient population.
Professor of Pulmonary and Critical Care Medicine at the University of Pittsburgh and chief investigator of the LUNA programme, Frank Sciurba said: “These results add to the growing body of evidence that indicates tozorakimab delivered meaningful clinical benefits for COPD patients who urgently need new treatment options.
“Up to half of patients today still experience exacerbations even when taking standard-of-care inhaled therapies.”
Tozorakimab was reported to be generally well tolerated, with a safety profile consistent with previous studies.
The monoclonal antibody targets interleukin-33 (IL-33), a cytokine involved in inflammatory pathways associated with COPD. It is designed to inhibit signalling from both reduced and oxidised forms of IL-33, with the aim of reducing inflammation and disrupting mucus dysfunction linked to disease progression.
COPD affects nearly 400 million people globally and is the third leading cause of death worldwide. Despite existing inhaled therapies, more than half of patients continue to experience exacerbations, which are associated with increased risks of hospitalisation, cardiopulmonary events and mortality.
AstraZeneca said the MIRANDA data will be submitted to regulatory authorities and presented at an upcoming medical meeting. Tozorakimab is also being evaluated in phase 3 trial for severe viral lower respiratory tract disease and in a phase 2 trial for asthma.