Itepekimab Cuts Exacerbations 27.1% in AERIFY-1 but Misses in AERIFY-2
REGN•Regeneron and Sanofi’s Phase III AERIFY-1 trial showed itepekimab reduced COPD exacerbations by 27.1% (q2w) and 20.5% (q4w), but AERIFY-2 failed to reach statistical significance, with only 1.6% and 12.4% reductions. These conflicting outcomes threaten FDA approval prospects for itepekimab in COPD.
1. Trial Designs and Patient Populations
On May 16, Sanofi and Regeneron presented AERIFY-1 and AERIFY-2 Phase III trials evaluating itepekimab in former smokers with moderate to severe COPD. Both studies enrolled patients with a history of at least 10 pack-years, tested 300mg itepekimab every two weeks and every four weeks, and AERIFY-2 included a small active smoking subgroup.
2. Efficacy Results in AERIFY-1 vs AERIFY-2
AERIFY-1 achieved statistically significant annualised reductions in moderate or severe exacerbations of 27.1% with biweekly dosing and 20.5% with monthly dosing. In contrast, AERIFY-2 saw only 1.6% reduction with biweekly dosing and 12.4% with monthly dosing, neither reaching significance; severe treatment-emergent adverse events averaged 17–18% across both trials.
3. Regulatory Implications and Competitive Landscape
The lack of replicated efficacy in AERIFY-2 undermines the case for FDA approval based on a single positive trial. AstraZeneca’s anti-IL-33 candidate tozorakimab, which met primary endpoints in two Phase III COPD studies with consistent exacerbation reductions, appears positioned to lead the market ahead of itepekimab.
