Tozorakimab Reduces COPD Exacerbations in Phase 3 Trials

Tozorakimab (MEDI3506) met its primary and key secondary end points in the Phase 3 OBERON (NCT05166889) and TITANIA (NCT05158387) trials, significantly reducing the annualized rate of moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations compared with placebo.¹

The investigational anti–IL-33 monoclonal antibody was studied as an add-on to inhaled standard-of-care maintenance therapy in patients with a history of exacerbations, regardless of smoking status or blood eosinophil count. Full results were published concurrently in the New England Journal of Medicine and presented at the European Respiratory Society (ERS) Congress 2026.^1,2

Exacerbation Rates Fell in Both Trials

Among former smokers, the prespecified primary end point in both trials, tozorakimab reduced the annualized rate of moderate or severe exacerbations by 29% in OBERON (rate ratio [RR], 0.71; 95% CI, 0.57-0.88; P = .002) and by 34% in TITANIA (RR, 0.66; 95% CI, 0.55-0.80; P < .001), compared with placebo. In the overall population of current and former smokers, the first key secondary end point, the annualized rate fell by 30% in OBERON (RR, 0.70; 95% CI, 0.58-0.85; P < .001) and by 29% in TITANIA (RR, 0.71; 95% CI, 0.59-0.84; P < .001).^1,2

OBERON randomized 446 patients to tozorakimab and 431 to placebo, and TITANIA randomized 438 patients to tozorakimab and 435 to placebo. Patients received 300 mg of subcutaneous tozorakimab or placebo every 4 weeks for 52 weeks, added to stable background maintenance therapy that included triple inhaled therapy in more than 90% of participants in each trial.²

"The OBERON and TITANIA trials mark the first time we have seen a biologic in COPD achieve efficacy in a broad population across blood eosinophil thresholds, including in patients with baseline eosinophils below 150, and irrespective of smoking status," Frank Sciurba, MD, FCCP, professor of pulmonary and critical care medicine at the University of Pittsburgh and chief investigator of the LUNA program, said in a news release.¹ "These unprecedented results, along with its favorable safety profile, underscore tozorakimab's potential as an innovative treatment for the millions of people living with COPD who remain at risk despite treatment with inhaled standard of care."

Benefit Extends Beyond Elevated Eosinophil Counts

In a pooled subgroup analysis of both trials, tozorakimab reduced exacerbations across eosinophil thresholds. A 43% reduction among patients with blood eosinophil counts of 300 cells/µL or higher (RR, 0.57; 95% CI, 0.44-0.74), a 34% reduction among those with counts of 150 cells/µL or higher (RR, 0.66; 95% CI, 0.56-0.78), and a 23% reduction among those with counts below 150 cells/µL (RR, 0.77; 95% CI, 0.62-0.94). Dupilumab and mepolizumab, the biologics currently approved for COPD, are indicated only for patients with elevated blood eosinophil counts, leaving a gap in treatment options for the broader COPD population.^1,2

Tozorakimab is a first-in-class monoclonal antibody that inhibits IL-33 signaling through both its reduced and oxidized forms, acting on the ST2 (serum-stimulated 2) receptor and the receptor for advanced glycation end products/epidermal growth factor receptor (RAGE/EGFR) complex, respectively.^1,3

Dysregulated IL-33 signaling through these pathways has been implicated in the airway inflammation and mucus dysfunction that drive COPD exacerbations.^2,3 In an integrated analysis, tozorakimab also reduced patients' mucus plug scores, which AstraZeneca said made it the first biologic shown to reduce mucus plugging in a broad population of patients with COPD.¹

"Today's groundbreaking tozorakimab results, from 2 replicate trials, set a new standard for COPD treatment outcomes in a broad population of patients," Sharon Barr, executive vice president, BioPharmaceuticals Research and Development at AstraZeneca, said in a news release.¹ "AstraZeneca has clinically validated the novel approach of targeting the signalling of the 2 forms of IL-33 to both decrease inflammation and disrupt the cycle of mucus dysfunction. With our FDA Priority Review, we look forward to bringing this treatment to patients as quickly as possible."

Adverse events occurred in 70.4% of patients receiving tozorakimab and 77.2% of those receiving placebo in OBERON, and in 80.1% and 79.8%, respectively, in TITANIA. Serious adverse events were reported in 23.3% of the tozorakimab group and 27.0% of the placebo group in OBERON and in 31.1% and 32.4%, respectively, in TITANIA.²

According to AstraZeneca, the only adverse drug reaction identified in either trial was injection-site reaction, which occurred more frequently with tozorakimab (6.5% in OBERON, 9.8% in TITANIA) than with placebo (3.3% in OBERON, 4.6% in TITANIA).^1,2

Implications for Pharmacists

COPD affects approximately 16 million adults in the United States, and COPD-related hospitalizations account for nearly 50% of the disease's direct medical costs. In the US, exacerbations cause more than 2500 emergency department visits daily, and only 50% of patients survive more than 3.5 years after a first severe exacerbation.^1,4

Pharmacists already play an established role in COPD management, including medication reconciliation, inhaler technique training, spirometry screening, smoking cessation counseling, and vaccination advocacy, all of which support treatment adherence alongside emerging biologic therapies.⁴

Pharmacist-led interventions have been shown to reduce hospital readmissions and drug-related events in patients with COPD, positioning pharmacists to help identify appropriate candidates for add-on biologic therapy and counsel patients on the every-4-week injection schedule tozorakimab would require, if approved.⁴

REFERENCES

1. AstraZeneca. Tozorakimab demonstrated statistically significant and highly clinically meaningful reduction in COPD exacerbations in OBERON and TITANIA Phase III trials. News release. AstraZeneca. September 8, 2026. Accessed September 8, 2026. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2026/Tozorakimab-demonstrated-statistically-significant-and-highly-clinically-meaningful-reduction-in-COPD-exacerbations-in-OBERON-and-TITANIA-Phase-III-trials.html

2. Sciurba FC, Watz H, Bourdin A, et al. Tozorakimab to Prevent COPD Exacerbations. N Engl J Med. Published online September 8, 2026. doi:10.1056/NEJMoa2606998

3. England E, Rees DG, Scott IC, et al. Tozorakimab (MEDI3506): an anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE/EGFR to reduce inflammation and epithelial dysfunction. Sci Rep. 2023;13(1):9825. Published 2023 Jun 17. doi:10.1038/s41598-023-36642-y

4. Hudd TR. Emerging role of pharmacists in managing patients with chronic obstructive pulmonary disease. Am J Health Syst Pharm. 2020;77(19):1625-1630. doi:10.1093/ajhp/zxaa216