Tozorakimab reduces COPD exacerbations in two large clinical trials
Benefits seen regardless of smoking history, disease severity, immune cell count
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The experimental therapy tozorakimab from AstraZeneca was superior to a placebo at reducing the rate of moderate to severe exacerbations, or sudden episodes of symptom worsening, in adults with chronic obstructive pulmonary disease (COPD).
That’s according to top-line, one-year data from two Phase 3 clinical trials — OBERON (NCT05166889) and TITANIA (NCT05158387) — that also showed the therapy’s benefits were seen regardless of a patient’s smoking history, lung disease severity, and the number of eosinophils, a type of immune cell linked to COPD-related inflammation.
The biologic therapy, which blocks the immune signaling molecule interleukin-33 (IL-33), was also generally well tolerated and showed a favorable safety profile, according to the company. Biologics are medications derived from living organisms.
“Today’s tozorakimab results deliver the first two confirmatory Phase [3] trials for an IL-33 biologic, which is a major scientific advancement in COPD, the world’s third leading cause of death,” Sharon Barr, executive vice president of biopharmaceuticals research and development at AstraZeneca, said in a company press release.
‘Meaningful clinical benefit’
Confirmatory trials are designed to provide robust safety and efficacy data that can be used to support a therapy’s approval. AstraZeneca said it plans to share the full results from OBERON and TITANIA at an upcoming medical meeting.
“These trial results suggest that targeting the IL-33 pathway with tozorakimab delivers meaningful clinical benefit in a trial representing a broad COPD population, independent of smoking status and eosinophilic levels,” said Frank Sciurba, MD, professor of pulmonary and critical care medicine at the University of Pittsburgh and chief investigator of the Phase 3 tozorakimab program.
COPD is a chronic inflammatory lung disease commonly caused by long-term exposure to irritants such as cigarette smoke. It’s marked by blocked airways and symptoms such as cough with mucus, wheezing, and shortness of breath. Exacerbations, or flare-ups, are episodes when symptoms suddenly worsen. These are common and can last for several days, accelerating lung function decline, and reducing physical function and quality of life, and sometimes requiring hospitalization.
Standard COPD treatment relies on inhaled therapies, such as bronchodilators, to open the airways. Even with these, however, more than half of patients continue to have exacerbations.
Administered by injections under the skin, tozorakimab is an antibody-based biologic that targets both existing versions of IL-33, a signaling molecule that helps drive ongoing airway inflammation in COPD.
IL-33 is released by airways cells in response to cellular stress or damage, such as that caused by cigarette smoke, allergens, or environmental pollutants, which in turn initiate and amplify multiple inflammatory cascades.
“Tozorakimab works in a fundamentally different way from other biologics, [blocking] the signaling of the reduced and oxidized forms of IL-33 to both decrease inflammation and disrupt the cycle of mucus dysfunction that are key disease drivers in COPD,” Barr said.
Reducing COPD exacerbations
OBERON and TITANIA were designed as two global, parallel trials to evaluate tozorakimab’s safety and efficacy in adults, aged 40 and older, with symptomatic COPD and who had a history of at least two moderate or one severe exacerbation in the year before enrolling.
Across both studies, 2,306 participants were randomly assigned to receive an injection of either tozorakimab or a placebo, once every four weeks for 52 weeks, on top of standard inhaled therapy. All had been receiving inhaled maintenance therapy for at least three months before entering the trials.
The main goal of both trials was to assess whether tozorakimab could reduce the annual rate of moderate-to-severe exacerbations in former smokers. A key secondary goal evaluated changes in exacerbation rates in the overall population, including both former and current smokers.
According to AstraZeneca, top-line results showed tozorakimab met the main and key secondary goal in both studies, and was associated with “statistically significant and highly clinically meaningful reductions in COPD exacerbations.” Also, the benefits were consistent across patients with different blood eosinophil counts and across all stages of disease severity, and the therapy was found to be generally safe and well tolerated.
“COPD has long been a difficult-to-treat disease with inherent heterogeneity and significant unmet need, with up to half of patients worldwide at risk of exacerbations, hospitalizations, cardiopulmonary events, and death — underscoring the importance of these results for advancing COPD science,” Sciurba said.
The Phase 3 tozorakimab program, called LUNA, also includes two other trials, PROSPERO (NCT05742802) and MIRANDA (NCT06040086). PROSPERO is an extension study designed to enroll participants who complete OBERON or TITANIA to assess the therapy’s long-term safety and effectiveness. MIRANDA is testing the therapy, administered every two weeks, against a placebo in 1,454 adults with symptomatic COPD and a history of exacerbations. Results from both are expected in the coming months.
