Regeneron, Sanofi: AERIFY-1 Phase 3 trial of itepekimab met primary endpoint

Regeneron Pharmaceuticals (REGN) and Sanofi (SNY) announced that a Phase 3 trial, AERIFY-1, evaluating the investigational use of itepekimab in adults who were former smokers with inadequately controlled chronic obstructive pulmonary disease, met the primary endpoint of significantly reducing moderate or severe acute exacerbations by 27% compared to placebo at week 52, a clinically meaningful benefit. A second Phase 3 trial, AERIFY-2, did not meet the same primary endpoint, although a benefit was seen earlier in the trial. In the trials, patients were randomized to receive itepekimab every two weeks, every four weeks, or placebo, 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. The total number of exacerbations was lower than prospectively anticipated, decreasing the power of both trials. Enrollment largely occurred during the time of the global COVID-19 pandemic, which could have contributed to the lower overall exacerbation rates. The safety profile of itepekimab was consistent across dosing regimens, and adverse events were generally comparable between treatment and placebo groups. In AERIFY-1, the overall rates of AEs were 67% and 68% for itepekimab every two weeks and every four weeks, respectively, compared to 68% for placebo. In AERIFY-2, the overall rates of AEs were 64% and 71% for itepekimab every two weeks and every four weeks, respectively, compared to 64% for placebo. In AERIFY-1, the rate of serious infections was 7% for each itepekimab arm, compared to 10% for placebo. In AERIFY-2, the rate of serious infections was 10% and 7% for itepekimab every two weeks and every four weeks, respectively, compared to 7% for placebo. AEs leading to death were 1% for each itepekimab arm compared to 2% for placebo in AERIFY-1, and 3% for each itepekimab arm compared to 2% for placebo in AERIFY-2. The safety profile of itepekimab observed in the Phase 3 trials was consistent with prior clinical trials. Anti-drug antibodies were rare and had no apparent impact on itepekimab drug levels.