The MIRANDA study found tozorakimab significantly lowered the rate of moderate-to-severe respiratory worsening in patients regardless of smoking history or specific white blood cell counts.
RT’s Three Key Takeaways:
- Exacerbation Reduction: The Phase III MIRANDA trial demonstrated that tozorakimab significantly reduced the annualized rate of moderate-to-severe COPD exacerbations in both former and current smokers.
- Unique Mechanism: Tozorakimab acts as a potential first-in-class monoclonal antibody targeting interleukin-33 to address both lung inflammation and mucus dysfunction.
- Broad Clinical Application: Positive results were observed across all blood eosinophil counts and all stages of lung function severity, suggesting benefits for a wide range of patients who remain symptomatic on standard inhaled therapies.
AstraZeneca announced positive high-level results from the pivotal Phase III MIRANDA trial, which demonstrated that tozorakimab significantly reduced the annualized rate of moderate-to-severe COPD exacerbations. The trial met its primary endpoint by showing a statistically significant and clinically meaningful reduction in flare-ups among former smokers, as well as in the overall population of former and current smokers.
The study evaluated a 300 mg dose of tozorakimab administered every two weeks compared to a placebo. Participants in the trial remained symptomatic and experienced moderate-to-severe exacerbations despite receiving standard of care inhaled therapies. The results showed consistent benefits across all stages of lung function severity and all blood eosinophil counts, which are white blood cells that can contribute to respiratory inflammation.
“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,” said Frank Sciurba, professor of pulmonary and critical care medicine at the University of Pittsburgh and chief investigator of the LUNA program. Sciurba noted that up to half of patients currently experience exacerbations while on standard inhaled treatments, increasing the risk of hospitalization and death.
Tozorakimab is a human monoclonal antibody that binds to interleukin-33 (IL-33). By inhibiting the signaling of both reduced and oxidized forms of IL-33, the biologic aims to reduce inflammation and disrupt the cycle of mucus dysfunction that contributes to the progression of COPD.
“These data further demonstrate tozorakimab’s exciting potential as a first-in-class biologic with a truly differentiated mechanism of action that inhibits the signalling of the reduced and oxidised forms of IL-33 to address underlying drivers of COPD,” said Sharon Barr, executive vice president of biopharmaceuticals R&D at AstraZeneca.
The safety profile of tozorakimab in the MIRANDA trial was favorable and consistent with previous clinical studies. These findings follow the March 2026 announcement of positive results from the OBERON and TITANIA Phase III trials, which investigated tozorakimab using a four-week dosing interval.
COPD currently affects nearly 400 million people and is the third leading cause of death worldwide. In the US, exacerbations account for more than 2,500 emergency department visits every day. Tozorakimab previously received Fast Track Designation from the Food and Drug Administration (FDA) for the treatment of COPD in December 2024.
AstraZeneca stated that the MIRANDA data will be submitted to regulatory authorities and presented to the scientific community at an upcoming medical meeting. The biologic is also being studied in Phase III trials for severe viral lower respiratory tract disease and Phase II trials for asthma.
