Tozorakimab Cut COPD Exacerbations in OBERON and TITANIA

Key Takeaways

• Among former smokers with chronic obstructive pulmonary disease (COPD) and previous exacerbations despite stable inhaled maintenance therapy, add-on tozorakimab significantly lowered annualized moderate or severe exacerbation rates versus placebo in both trials.
• The first key secondary comparison also found significantly lower rates in the combined population of current and former smokers, without separately establishing an effect in current smokers.
• Any adverse event occurred with tozorakimab versus placebo in 70.4% versus 77.2% of OBERON participants and 80.1% versus 79.8% of TITANIA participants.

Sciurba and colleagues conducted the OBERON and TITANIA phase 3 trials, which randomized adults with COPD who currently or formerly smoked and had exacerbations in the previous year despite stable standard-of-care inhaled maintenance therapy. Participants received add-on subcutaneous tozorakimab 300 mg, which inhibits IL-33 activity, or placebo every four weeks for 52 weeks. The primary endpoint was annualized moderate or severe exacerbations over 52 weeks among former smokers. The first key secondary endpoint measured the same outcome in current and former smokers combined, and safety was also assessed.

Among former smokers in OBERON, annualized moderate or severe exacerbation rates were 1.34 with tozorakimab versus 1.90 with placebo, with a rate ratio of 0.71 (95% confidence interval, 0.57–0.88), a significant difference. Among former smokers in TITANIA, annualized moderate or severe exacerbation rates were 1.37 with tozorakimab versus 2.07 with placebo per patient-year, with a rate ratio of 0.66 (95% confidence interval, 0.55–0.80), also a significant difference.

For the first key secondary endpoint, annualized moderate or severe exacerbation rates were significantly lower with tozorakimab in the combined current- and former-smoker population of each trial. The rate ratios were 0.70 in OBERON and 0.71 in TITANIA.

Adverse events occurred in 70.4% and 80.1% of patients with tozorakimab and 77.2% and 79.8% of patients in placebo in OBERON and TITANIA, respectively. Sciurba and colleagues concluded that add-on tozorakimab lowered moderate or severe COPD exacerbation rates versus placebo over the treatment period in the former-smoker primary and combined-population secondary analyses in both trials.

Clinician Questions

Was tozorakimab shown to reduce COPD exacerbations specifically in current smokers?

The primary comparison assessed former smokers, while the significant secondary finding pooled current and former smokers. That pooled finding does not isolate a treatment effect among current smokers alone.

Does tozorakimab’s COPD result establish efficacy at every blood eosinophil level?

Adults with COPD could enter OBERON and TITANIA without a blood-eosinophil-count eligibility cutoff. Unrestricted eligibility does not establish the effect of add-on tozorakimab within each individual eosinophil-count stratum.

Recommended Reading

• For more on COPD diagnostic challenges: Addressing Missed and Misdiagnosed COPD Cases
• For more on exacerbations in chronic airway disease: Bridging the Bronchiectasis Gap: The Latest Emerging Multimodal Treatment Approaches