Tozorakimab Improves Daily Respiratory Symptoms in COPD: OBERON, TITANIA

An analysis of the phase 3 OBERON and TITANIA trials presented at the CHEST Annual Meeting 2026 in Phoenix found tozorakimab improved patient-reported daily respiratory symptoms vs placebo in patients with COPD and a history of exacerbations.¹

Full results presented at the European Respiratory Society (ERS) Congress 2026 showed tozorakimab, an investigational anti-interleukin-33 (IL-33) monoclonal antibody, reduced moderate to severe exacerbations by 29% in OBERON and 34% in TITANIA among former smokers, the primary population.²,3 In the overall population of current and former smokers, reductions were 30% and 29%, respectively.² The new analysis asked whether the exacerbation benefit extends to how patients feel day to day.1

“Exacerbations are really important events in these patients’ lives, resulting in hospitalization, leading to other downstream effects, including death,” said lead investigator Frank Sciurba, MD, professor of medicine at the University of Pittsburgh School of Medicine and director of the Emphysema COPD Research Center, in an interview with HCPLive. “Patients do want to feel better, independent of [exacerbation] risk reduction.”

Tozorakimab E-RS:COPD Results in OBERON and TITANIA

Sciurba and colleagues analyzed 1750 current and former smokers randomized to subcutaneous tozorakimab 300 mg (n = 446 in OBERON; n = 438 in TITANIA) or placebo (n = 431; n = 435) every 4 weeks for up to 52 weeks.¹ The team assessed change from baseline in the Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total score (range, 0 to 40) and its subdomains for breathlessness, cough/sputum, and chest symptoms.¹ Daily scores were aggregated into 14-day intervals and analyzed with a repeated measures model.¹

Baseline mean E-RS:COPD total scores ranged from 14.4 to 15.2 across arms.¹ At week 52, the least-squares (LS) mean change from baseline was −2.31 (95% CI, −2.94 to −1.67) with tozorakimab vs −1.41 (95% CI, −2.05 to −0.77) with placebo in OBERON.¹ In TITANIA, the corresponding changes were −1.92 (95% CI, −2.45 to −1.40) and −0.84 (95% CI, −1.37 to −0.32), for LS mean differences vs placebo of −0.90 (95% CI, −1.54 to −0.26) in OBERON and −1.08 (95% CI, −1.66 to −0.50) in TITANIA.¹

Separation emerged after the first dose. At week 4, the LS mean difference was −0.62 (95% CI, −1.22 to −0.03) in TITANIA and −0.68 (95% CI, −1.40 to 0.04) in OBERON, where the CI crossed 0.1 Sciurba said the early timepoint was not powered for significance and noted the effect broadened across the 52-week treatment period.

Tozorakimab Effects on Breathlessness, Cough, and Chest Symptoms

Tozorakimab improved all 3 E-RS:COPD subdomains vs placebo at 52 weeks.¹ In OBERON, LS mean differences were −0.36 (95% CI, −0.66 to −0.05) for breathlessness, −0.16 (95% CI, −0.31 to −0.02) for cough/sputum, and −0.27 (95% CI, −0.44 to −0.09) for chest symptoms.¹ TITANIA showed differences of −0.38 (95% CI, −0.64 to −0.12), −0.18 (95% CI, −0.31 to −0.06), and −0.31 (95% CI, −0.47 to −0.15), respectively.¹

In the pooled population, total score changes favored tozorakimab across screening blood eosinophil subgroups: −0.60 (95% CI, −1.20 to 0.01) for < 150 cells/µL, −0.82 (95% CI, −1.30 to −0.33) for ≥ 150 cells/µL, and −0.71 (95% CI, −1.47 to 0.06) for ≥ 300 cells/µL.¹ Sciurba said symptom benefit was also consistent across lung function severity, chronic bronchitis status, and smoking status. He noted exacerbation reductions of about 23% in patients with fewer than 150 eosinophils/µL and about 43% in those with 300 cells/µL or more.

Placebo groups also improved across 52 weeks, a pattern Sciurba attributed to the placebo effect and regression to the mean common in COPD trials. He emphasized the separation between arms, which he described as early and durable through week 52. Sciurba also called the consistency across smoking status unexpected, since earlier data with a competing IL-33 pathway agent suggested reduced efficacy in active smokers.

“In patients who have a history of frequent exacerbations, this drug offers not only in the Th2-high space another potential product to try, but also in a space where there currently is a large unmet need,” Sciurba said. “It reduces exacerbation risk but also improves symptoms, which is important to patients in both Th2-high and Th2-low subgroups.”

AstraZeneca reported tozorakimab was generally well tolerated in both trials.² The FDA accepted the company’s Biologics License Application for tozorakimab 300 mg as add-on maintenance treatment for adults with COPD under Priority Review, with a decision anticipated in the first quarter of 2027.²

Sciurba’s disclosures include AstraZeneca and others.

References

1. Sciurba FC, Bhatt SP, Watz H, et al. Tozorakimab treatment improves daily respiratory symptoms in patients with chronic obstructive pulmonary disease: results from the OBERON and TITANIA studies. Presented at CHEST Annual Meeting 2026; October 18-21, 2026; Phoenix, AZ.

2. Tozorakimab demonstrated statistically significant and highly clinically meaningful reduction in COPD exacerbations in OBERON and TITANIA phase III trials. AstraZeneca. Published September 8, 2026. Accessed October 21, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/tozorakimab-demonstrated-statistically-significant-highly-clinically-meaningful-reduction-copd-exacerbations-oberon-titania-phase-iii-trials.html

3. Sciurba F. Tozorakimab Cuts COPD Exacerbations Across Eosinophil Levels: Frank Sciurba, MD. HCPLive. Published September 8, 2026. Accessed October 21, 2026. https://www.hcplive.com/view/tozorakimab-cuts-copd-exacerbations-across-eosinophil-levels