An Add-On Shot Cut Flare-Ups in People Whose COPD Inhalers Were Not Enough

Two matched phase 3 trials of tozorakimab, an antibody given as an injection under the skin, reported fewer flare-ups of chronic obstructive pulmonary disease than placebo, in results published in the New England Journal of Medicine on September 8.

Many people with COPD keep having flare-ups even on standard inhaled maintenance treatment, the authors write, and the drug was tested as an add-on for exactly that group. Tozorakimab blocks interleukin-33, an immune signaling protein the authors say is involved in how the disease develops.

The two AstraZeneca-funded trials, OBERON and TITANIA, ran the same design. Adults with COPD who had a history of flare-ups in the previous year were randomly assigned to tozorakimab 300 mg or placebo every four weeks for 52 weeks, on top of their usual inhalers. There was no eligibility limit on blood eosinophil count, a type of white blood cell. OBERON assigned 446 patients to the drug and 431 to placebo, TITANIA 438 and 435.

The main test in both trials was the annualized rate of moderate or severe flare-ups among former smokers, counted as events per patient per year. In OBERON that rate was 1.34 on tozorakimab against 1.90 on placebo, a rate ratio of 0.71 (95% CI, 0.57 to 0.88). In TITANIA it was 1.37 against 2.07, a rate ratio of 0.66 (95% CI, 0.55 to 0.80).

In the overall population of current and former smokers (the trials' first key secondary endpoint), the rate ratios were 0.70 in OBERON and 0.71 in TITANIA.

Adverse events were reported in 70.4% of patients on tozorakimab and 77.2% of those on placebo in OBERON, and in 80.1% and 79.8% in TITANIA.

The first author is Frank C. Sciurba of the University of Pittsburgh and the senior author Ioannis Psallidas of AstraZeneca; company employees are among the co-authors. The trials are registered as NCT05166889 (OBERON) and NCT05158387 (TITANIA).