ITEPEKIMAB reduced COPD exacerbations in one Phase III trial, but the effect was not replicated across AERIFY-2.
Itepekimab COPD Results From AERIFY
Late breaking Phase III data from AERIFY-1 and AERIFY-2 showed mixed efficacy for itepekimab in former smokers with chronic obstructive pulmonary disease (COPD), highlighting both the promise and uncertainty of targeting IL-33 signaling in this population.
Itepekimab, a fully human monoclonal antibody designed to inhibit IL-33 signaling, was assessed as an add-on therapy in two multinational, randomized, double-blind, placebo-controlled trials. Both studies enrolled former smokers aged 40–85 years with physician-diagnosed COPD for at least 1 year, moderate-to-severe airflow limitation, and a history of at least two moderate exacerbations or one severe exacerbation in the previous year despite dual or triple inhaler therapy.
Patients received subcutaneous itepekimab 300 mg every 2 weeks, itepekimab 300 mg every 4 weeks, or placebo for 52 weeks. The primary endpoint was the annualized rate of moderate or severe exacerbations, while a key secondary endpoint assessed change from baseline in pre-bronchodilator FEV1 at Week 24.
Exacerbation Reduction Was Not Replicated
In AERIFY-1, itepekimab significantly reduced moderate or severe COPD exacerbation rates compared with placebo. The every-2-weeks regimen reduced exacerbations by 27.1% versus placebo, while the every-4-weeks regimen reduced exacerbations by 20.5%.
However, this effect was not reproduced in AERIFY-2. In the second trial, itepekimab reduced exacerbations by 1.6% with the every-2-weeks regimen and by 12.4% with the every-4-weeks regimen, neither of which reached statistical significance.
Lung Function and Safety Findings
FEV1 findings also differed between the trials. In AERIFY-1, no meaningful improvement in pre-bronchodilator FEV1 was observed at Week 24, with least squares mean differences versus placebo of 6 mL and 10 mL for the every-2-weeks and every-4-weeks regimens, respectively.
In AERIFY-2, itepekimab significantly improved pre-bronchodilator FEV1 at Week 24, with least squares mean differences versus placebo of 38 mL for every 2 weeks and 75 mL for every 4 weeks.
Treatment-emergent adverse events were broadly comparable across treatment and placebo groups. In AERIFY-1, adverse events occurred in 67.1% of patients receiving itepekimab every 2 weeks, 68.2% receiving itepekimab every 4 weeks, and 68.4% receiving placebo. In AERIFY-2, rates were 64.3%, 71.2%, and 64.2%, respectively.
In current smokers evaluated in AERIFY-2, itepekimab every 2 weeks reduced moderate or severe exacerbations by 7.1% versus placebo, with a similar safety profile to that seen in former smokers.
Overall, the AERIFY trials suggest an acceptable safety profile for itepekimab in COPD, but the discordant efficacy findings leave its clinical role uncertain.
Reference
Klaus F. Rabe et al. Efficacy and Safety of Itepekimab in Former Smokers With Chronic Obstructive Pulmonary Disease: AERIFY-1 and AERIFY-2 Trials. ATS International Conference, 2026.
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