Tozorakimab reduced COPD flare-ups in top-line Phase 3 trial data
AstraZeneca reports benefits across patient groups in MIRANDA study
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One year of treatment with tozorakimab, AstraZeneca’s experimental therapy, was reported to significantly reduce the annual rate of moderate-to-severe exacerbations, or periods of sudden symptom worsening, in adults with chronic obstructive pulmonary disease (COPD).
These are the top-line results from the global Phase 3 MIRANDA clinical trial (NCT06040086), which tested a 300 mg dose of tozorakimab once every two weeks against a placebo, on top of standard of care. The reported benefits were seen in former smokers and in the overall study population, which included both former and current smokers, as well as across blood eosinophil counts and all stages of lung function severity. Eosinophils are immune cells associated with inflammation in COPD.
MIRANDA marks third positive late-stage COPD trial
These findings follow previously announced positive top-line results from two other global Phase 3 clinical studies, OBERON (NCT05166889) and TITANIA (NCT05158387), showing that tozorakimab at a four-week dosing interval was superior to a placebo at reducing moderate-to-severe COPD exacerbations.
“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,” Frank Sciurba, MD, professor at the University of Pittsburgh and chief investigator of the tozorakimab Phase 3 program, called LUNA, said in a press release from AstraZeneca.
“We look forward to sharing the data with regulators and the scientific community as soon as possible,” said Sharon Barr, executive vice president of biopharmaceuticals R&D at AstraZeneca.
A chronic inflammatory condition, COPD obstructs airflow and can cause shortness of breath, wheezing, and cough with mucus. The disease is commonly linked to long-term exposure to lung irritants, including tobacco smoke and air pollution, and is punctuated by exacerbations. These sudden flare-ups can accelerate declines in lung function while significantly impairing a patient’s daily activity and overall well-being.
Many patients still have flare-ups on inhaled COPD therapies
Standard COPD treatment often includes bronchodilators, which widen the airways, and may include inhaled corticosteroids — anti-inflammatory medications that can cause side effects when used long term.
However, “up to half of patients today still experience exacerbations even when taking standard-of-care inhaled therapies, putting them at risk of serious health consequences including hospitalization and even death,” Sciurba said.
Tozorakimab is designed to block signaling from two forms (reduced and oxidized) of IL-33, a signaling molecule that contributes to ongoing airway inflammation in COPD. IL-33 can be released in response to airway stress or damage, helping initiate and amplify inflammatory responses.
The MIRANDA trial, involving more than 350 clinical sites around the world, was designed to test tozorakimab in adults, 40 years and older, with symptomatic COPD and a history of two or more moderate exacerbations or one severe exacerbation in the previous year.
The study enrolled a total of 1,454 patients who had been on inhaled maintenance therapy for the previous three or more months. These were randomly assigned to receive either tozorakimab (300 mg) or a placebo via an under-the-skin injection, once every other week for 52 weeks (about one year), on top of standard inhaled therapy.
Top-line data show fewer moderate-to-severe flare-ups
MIRANDA’s main goal was to determine if the experimental therapy was superior to the placebo at reducing the annual rate of moderate-to-severe exacerbations in participants who were former smokers. Differences in exacerbation rates in the overall population, which included both former and current smokers, were a key secondary endpoint.
AstraZeneca reported that both the main and key secondary endpoints were attained, with tozorakimab leading to “a statistically significant and clinically meaningful reduction in the annualized rate of moderate-to-severe COPD exacerbations in the primary population of former smokers and in the overall population,” the release stated.
According to AstraZeneca, tozorakimab’s superiority over the placebo was also seen across all stages of lung function severity and blood eosinophil counts. In addition, tozorakimab showed a favorable safety profile that was consistent with that seen in previous trials.
“These data further demonstrate tozorakimab’s exciting potential as a first-in-class biologic with a truly differentiated mechanism of action that inhibits the signaling of the reduced and oxidized forms of IL-33 to address underlying drivers of COPD,” Barr said.
In addition to MIRANDA, OBERON, and TITANIA, the LUNA program includes PROSPERO (NCT05742802), a randomized long-term extension study of patients who completed OBERON or TITANIA, designed to evaluate severe COPD exacerbations over up to two years.
