Sanofi and Regeneron’s experimental COPD drug, itepekimab, produced mixed results in two Phase 3 trials, raising serious questions about its chances of regulatory approval. While one of the late-stage studies showed significant benefits in reducing exacerbations of chronic obstructive pulmonary disease (COPD), the other failed to meet its primary endpoint—putting the treatment’s future in jeopardy.
The trials, AERIFY-1 and AERIFY-2, evaluated the efficacy of itepekimab in around 2,000 former smokers aged 40–85 with moderate-to-severe COPD. In AERIFY-1, the drug significantly reduced moderate and severe COPD flare-ups by 27% with biweekly dosing and 21% with monthly dosing over 52 weeks. However, AERIFY-2 did not replicate the success—reporting only a 2% reduction with biweekly dosing and 12% with monthly dosing, neither of which was statistically significant.
The diverging outcomes have prompted industry analysts to speculate that Sanofi and Regeneron may need to conduct a third Phase 3 trial, delaying potential market entry and increasing development costs. Brian Skorney of Baird emphasized that regulatory agencies typically expect two positive Phase 3 trials for approval. RBC Capital Markets’ Brian Abrahams echoed this, suggesting that pinpointing the causes of the inconsistent results could help strengthen the case in a future study, though uncertainty would persist.
The results come at a critical time for both companies—Regeneron is grappling with competition in its eye drug Eylea and preparing for the patent expiration of Dupixent, a top-selling inflammation therapy. Sanofi, meanwhile, is navigating similar commercial pressures.
Sanofi’s Head of R&D, Houman Ashrafian, acknowledged that while AERIFY-1’s results are encouraging, further research is needed to fully understand the drug’s mechanism—particularly the role of IL-33 inhibition in COPD. Both companies are currently analyzing the data and plan to consult with regulators.
A complicating factor, researchers say, is that COPD exacerbation rates in the studies were lower than expected, possibly due to pandemic-era enrollment, which may have reduced exposure to typical respiratory triggers. This has weakened the trials’ statistical power, making it more difficult to draw definitive conclusions between treatment groups.
Despite the setback, Sanofi and Regeneron remain committed to exploring itepekimab’s potential, but any future path to approval will likely be longer and more complex than originally planned.
