On 16 May, during the 2026 American Thoracic Society (ATS) International Conference, Sanofi and Regeneron presented new safety and efficacy data from their AERIFY-1 (NCT04701983) and AERIFY-2 (NCT04751487) Phase III clinical trials, evaluating itepekimab, a fully human interleukin-33 (IL-33) monoclonal antibody (mAb), in former smokers with moderate to severe chronic obstructive pulmonary disease (COPD).
The data presented at ATS supplemented findings released in 2024 from both trials, where only AERIFY-1 demonstrated statistically significant reductions in exacerbations—a discrepancy that remained unresolved and was not meaningfully clarified by the new data.
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AERIFY-1 and AERIFY-2 enrolled patients with a history of smoking 10 or more cigarette packs per year, with AERIFY-2 including a small subpopulation of patients who actively smoked 1 or more cigarettes per day on average. Both trials studied moderate and severe COPD patients with documented history of high exacerbation risks across two dosing arms, 300mg itepekimab every two weeks (q2w), and 300mg itepekimab every four weeks (q4w).
Findings presented at the ATS 2026 conference focused on patients with previous history of smoking (excluding current smokers) alone and were consistent with those reported in 2024. In AERIFY-1, annualised rates of moderate or severe exacerbations were significantly reduced compared with placebo, by 27.1% in the q2w dosing group and by 20.5% in the q4w dosing group.
In contrast, AERIFY-2 failed to replicate these results in the same population, with markedly attenuated reductions of just 12.4% in the q4w group and 1.6% in the q2w group, neither of which reached statistical significance compared to placebo. Across both trials, itepekimab was generally well tolerated, with severe treatment-emergent adverse events averaging between 17–18% between AERIFY-1 and -2 across the two dosing regimens.
The inconsistent results between AERIFY-1 and AERIFY-2 are likely to create a significant obstacle to US Food and Drug Administration (FDA) approval for itepekimab in COPD, as positive findings from a single trial are unlikely to be sufficient given how markedly AERIFY-2 failed to replicate them.
By contrast, AstraZeneca has recently reported positive topline results for its own anti-IL-33 mAb tozorakimab, where the drug met its primary endpoints in moderate to severe COPD in both OBERON (NCT05166889) and TITANIA (NCT05158387) Phase III clinical trials, significantly reducing exacerbation rates in both former smoking and current smoking patents, as per a 27 March 2026 press release. With tozorakimab demonstrating consistent efficacy across two replicate trials and a broader patient population, AstraZeneca appears well positioned to establish itself as the leading anti-IL-33 agent in COPD, leaving itepekimab with a significantly narrowed path in this indication.
Nevertheless, Sanofi and Regeneron retain a significant commercial foothold in the respiratory space through Dupixent (dupilumab), which received FDA and European Medicines Agency (EMA) approval for COPD in 2024 and is expected to continue to be a major driver of growth in the indication until impending loss of exclusivity. The COPD setback for itepekimab is therefore a pipeline disappointment rather than an existential commercial threat for the companies.
Beyond COPD, itepekimab remains a promising candidate for chronic rhinosinusitis with nasal polyps (CRSwNP), with a Phase III clinical trial (NCT06834347) actively recruiting patients, given the well-established role of IL-33 in driving type 2 airway inflammation, according to a 2017 article by Song and colleagues in ORL.
