Anti-IL-33 antibody tozorakimab cut COPD exacerbations by about 30%, without an eosinophil threshold

Design

Two replicate phase 3, randomised, double-blind, placebo-controlled trials (OBERON, TITANIA)

Population

About 1,750 adults with COPD and prior-year exacerbations on inhaled maintenance therapy

Primary outcome

Annualised moderate or severe exacerbations in former smokers over 52 weeks

Effect

Rate ratio 0.71 (95% CI 0.57–0.88) and 0.66 (0.55–0.80)

OBERON and TITANIA were replicate phase 3 trials in adults with COPD, current or former smokers, who had exacerbations in the past year despite standard inhaled maintenance therapy. Unlike existing COPD biologics, there was no blood eosinophil criterion. Patients received tozorakimab 300 mg or placebo subcutaneously every four weeks for 52 weeks; about 870 per trial.

In former smokers (the primary population), annual moderate or severe exacerbations fell from 1.90 to 1.34 (rate ratio 0.71, 95% CI 0.57 to 0.88) in OBERON and from 2.07 to 1.37 (0.66, 0.55 to 0.80) in TITANIA. In the overall population the rate ratios were 0.70 and 0.71. Adverse events were similar to placebo.

If approved, this would be among the first biologics for COPD that do not depend on type 2 inflammation. It was not approved by the FDA, EMA or CDSCO at the time of writing.

• Tozorakimab is investigational; it is not available for prescribing.
• Benefit did not require a raised blood eosinophil count, unlike existing COPD biologics.
• Before any biologic, confirm inhaler technique, adherence, smoking cessation and pulmonary rehabilitation.
• Record exacerbation frequency accurately; it defines who would qualify for add-on therapy.

Why it matters

It could open biologic treatment to COPD patients without eosinophilic disease, who currently have no such option.

Don't overread it

The drug was not approved by the FDA, EMA or CDSCO at the time of writing; these are trial results, not a licensed indication.

The statistics, in plain English

A rate ratio of 0.70 means about 30% fewer exacerbations per year. The absolute difference was about 0.6 exacerbations per patient per year. Two replicate trials with consistent results make chance an unlikely explanation.

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