Itepekimab Demonstrates Mixed Phase 3 Results for COPD Exacerbations

Itepekimab statistically significantly reduced moderate or severe exacerbations in former smokers with (COPD) regardless of eosinophilic phenotype, meeting the primary endpoint of the phase 3 AERIFY-1 trial, but not the primary endpoint of the similar AERIFY-2 trial.1

“COPD is a particularly complex disease, and novel approaches are needed to address the multiple underlying biological disease drivers,” George D. Yancopoulos, MD, PhD, Board co-Chair, President and Chief Scientific Officer at Regeneron, said in a statement.1 “We are proud of our work in this challenging treatment landscape, bringing Dupixent – the first-ever biologic medicine for COPD – to certain patients who previously had very limited options remaining. We are encouraged by the overall results from AERIFY-1 and the data through week 24 for AERIFY-2 and are reviewing the results from both itepekimab trials to inform next steps. We remain committed to our broader itepekimab development program and learnings from the AERIFY program will be invaluable as we continue to advance itepekimab in respiratory diseases with unmet need.”

Itepekimab significantly reduced moderate or severe acute exacerbations by 27% compared to placebo at week 52, a clinically meaningful benefit, in AERIFY-1. At the same time, Regeneron announced that its other randomized, Phase 3, double-blind, placebo-controlled trial evaluating itepekimab did not meet its primary endpoint, although a benefit was seen earlier in the trial. Both trials evaluated the efficacy and safety of itepekimab in 1,127 (AERIFY-1) and 953 (AERIFY-2) adults aged 40-85 years who were former smokers (who have not smoked for at least 6 months) with moderate-to-severe COPD.1

In both trials, patients were randomized to receive itepekimab every 2 weeks (AERIFY-1, n=375; AERIFY-2, n=326), every 4 weeks (AERIFY-1, n=377; AERIFY-2, n=303), or placebo (AERIFY-1, n=375; AERIFY-2, n=324), which was added to inhaled triple or double standard-of-care therapy. The primary endpoint for AERIFY-1 and AERIFY-2 was the reduction in the annualized rate of acute moderate or severe COPD exacerbations with itepekimab treatment.2

Regeneron noted that the total number of exacerbations was lower than prospectively anticipated, decreasing the power of both trials, possibly due to enrollment during the global COVID-19 pandemic, which could have contributed to the lower overall exacerbation rates.

Across both AERIFY-1 and AERIFY-2 trials, itepekimab showed a consistent safety profile, with overall adverse event (AE) rates similar between treatment and placebo groups (67–71% vs 64–68%). Serious infection rates were comparable or slightly lower with itepekimab (7–10%) vs placebo (7–10%), and AEs leading to death were low across arms (1–3% itepekimab vs 2% placebo). Anti-drug antibodies were rare and did not affect drug levels, aligning with prior trial findings.1

“While we are encouraged by the results of AERIFY-1, the results of both studies merit further exploration to have a full understanding of the data and the role that IL-33 plays in this complex disease,” Houman Ashrafian, MD, PhD, Executive Vice President, Head of Research and Development at Sanofi, added.1 “Certain people with COPD are in desperate need of new treatment options, especially those who continue to experience exacerbations despite being on maximal therapy, and we remain committed to discussing these data with regulatory agencies to evaluate our path forward.”

There are 2 additional ongoing trials in the program: AERIFY-3, a Phase 2 mechanistic study assessing the impact of itepekimab on airway inflammation in patients with COPD, and AERIFY-4, a Phase 3 trial assessing the long-term safety of itepekimab in patients with COPD.

REFERENCES

1. Itepekimab Met Primary Endpoint in One of Two Chronic Obstructive Pulmonary Disease (COPD) Phase 3 Trials. News release. Regeneron. May 30, 2025. https://www.globenewswire.com/news-release/2025/05/30/3090814/0/en/Itepekimab-Met-Primary-Endpoint-in-One-of-Two-Chronic-Obstructive-Pulmonary-Disease-COPD-Phase-3-Trials.html

2. Latest Dupixent® (dupilumab) and Itepekimab Data at ERS Highlight Scientific Innovation and Leadership in Respiratory Diseases. Regeneron. August 26, 2024. https://investor.regeneron.com/news-releases/news-release-details/latest-dupixentr-dupilumab-and-itepekimab-data-ers-highlight