Sanofi posts AERIFY-2 itepekimab COPD results: exacerbation rates in former smokers

Sanofi, with Regeneron Pharmaceuticals, has posted results for AERIFY-2, a Phase 3 study of itepekimab in adults with moderate-to-severe chronic obstructive pulmonary disease (COPD). The trial registry record for NCT04751487 lists the results as first posted on October 9, 2026. The record reports the annualized rate of moderate or severe exacerbations in former smokers as 0.879 on placebo and 0.770 on itepekimab every 4 weeks.

What the record says about the design

The record describes the study as randomized, double-blind, placebo-controlled and parallel-group. It lists itepekimab as SAR440340, also called REGN3500, and describes it as an anti-IL-33 mAb. The drug is given as a subcutaneous injection.

The record lists two cohorts. Former smokers were the primary population. They received placebo every 2 weeks, itepekimab 300 mg every 4 weeks with alternating placebo at the 2-week interval, or itepekimab 300 mg every 2 weeks, for up to 52 weeks. Current smokers received placebo or itepekimab 300 mg every 2 weeks for 52 weeks.

The record lists 1234 participants in total. In the former smoker cohort, 324 were assigned to placebo, 303 to itepekimab every 4 weeks and 326 to itepekimab every 2 weeks. In the current smoker cohort, 139 were assigned to placebo and 142 to itepekimab every 2 weeks.

According to the record, the study ran at 279 centers in 29 countries. It says 2512 participants were screened from 12-Feb-2021 to 15-May-2024, and 1273 were screen failures. The record lists the study start as February 12, 2021, primary completion as April 21, 2025 and completion as August 28, 2025.

The primary outcome

The primary outcome in the record is the annualized rate of adjudicated moderate or severe acute exacerbation events in the former smoker cohort over the 52-week placebo-controlled treatment period. The record counts a moderate exacerbation as an acute worsening of respiratory symptoms that required systemic corticosteroids, antibiotics or both. It counts a severe exacerbation as one that required hospitalization, observation for more than 24 hours in an emergency department or urgent care facility, or resulted in death.

The record reports the rate in exacerbations per participant-year, with 95% confidence intervals:

placebo: 0.879 (0.732 to 1.054)
itepekimab 300 mg every 4 weeks: 0.770 (0.636 to 0.932)
itepekimab 300 mg every 2 weeks: 0.865 (0.721 to 1.037)

The record compares each itepekimab group with placebo using a negative binomial regression model. For the every-4-weeks group, the rate ratio is 0.876 (95% confidence interval 0.710 to 1.081), with a p-value of 0.2176. For the every-2-weeks group, the rate ratio is 0.984 (95% confidence interval 0.803 to 1.206), with a p-value of 0.8781.

The record states that a hierarchical testing procedure controlled the overall type I error, and that the primary outcome was tested at a 2-sided significance level of 0.049. Both p-values above are higher than that level.

Severe exacerbations

The record lists the annualized rate of adjudicated severe exacerbations in former smokers as a secondary outcome. The rates were 0.105 on placebo (95% confidence interval 0.066 to 0.167), 0.096 on itepekimab every 4 weeks (0.059 to 0.157) and 0.113 on itepekimab every 2 weeks (0.072 to 0.178).

The rate ratio against placebo was 0.914 (95% confidence interval 0.548 to 1.526) with a p-value of 0.7315 for the every-4-weeks group. It was 1.075 (95% confidence interval 0.653 to 1.769) with a p-value of 0.7753 for the every-2-weeks group.

Safety counts in the record

The record reports deaths and serious adverse events for the safety population of the former smoker cohort. The record lists the number of participants who died as 9 of 321 on placebo, 11 of 302 on itepekimab every 4 weeks and 10 of 325 on itepekimab every 2 weeks. It lists the number of participants with serious adverse events as 72 of 321 on placebo, 74 of 302 on itepekimab every 4 weeks and 74 of 325 on itepekimab every 2 weeks.

Sanofi posted these figures as summary data in the registry. The record is the sponsor's report, and this story reports its numbers as posted.