Key Highlights
- AERIFY-1 met its primary endpoint, showing a 27% reduction in moderate or severe acute exacerbations at Week 52 in former smokers with COPD.
- AERIFY-2 did not meet the same endpoint, though early benefits were observed.
- Both studies evaluated itepekimab, a monoclonal antibody targeting interleukin-33 (IL33), believed to drive lung inflammation in former smokers.
- Sanofi and Regeneron continue to assess next steps with regulators.
About the AERIFY Trials
The AERIFY-1 and AERIFY-2 studies were large-scale, randomized, double-blind, placebo-controlled Phase 3 trials evaluating itepekimab in former smokers aged 40–85 years with moderate-to-severe chronic obstructive pulmonary disease (COPD). Patients received subcutaneous itepekimab every two or four weeks or a placebo, in addition to standard-of-care inhaled therapies (ICS, LABA, LAMA).
- AERIFY-1 (n=1,127): Met the primary endpoint with a statistically significant 27% reduction in the annualized rate of moderate or severe COPD exacerbations.
- AERIFY-2 (n=953): Did not meet the same endpoint, though early signs of benefit were reported.
Lower-than-expected exacerbation rates, possibly influenced by the COVID-19 pandemic, may have affected the statistical power of both trials.
Safety Profile and Adverse Events
Itepekimab showed a consistent safety profile across both dosing regimens and trials, with adverse events (AEs) generally comparable to placebo.
AERIFY-1:
- AEs: 67% (Q2W), 68% (Q4W), vs 68% (placebo)
- Serious infections: 7% (both arms) vs 10% (placebo)
- Deaths: 1% (both arms) vs 2% (placebo)
AERIFY-2:
- AEs: 64% (Q2W), 71% (Q4W), vs 64% (placebo)
- Serious infections: 10% (Q2W), 7% (Q4W), vs 7% (placebo)
- Deaths: 3% (both arms) vs 2% (placebo)
Anti-drug antibodies were rare and had no impact on drug levels.
Expert Commentary
“While we are encouraged by AERIFY-1, both studies require deeper exploration. COPD patients with persistent exacerbations need new treatment options, and we remain committed to advancing this program.”
- Houman Ashrafian, MD, PhD, EVP, Head of R&D at Sanofi.
“COPD is a biologically complex disease. We are reviewing all data carefully and continue to invest in itepekimab as a potential therapy across multiple respiratory indications.”
- George D. Yancopoulos, M.D., Ph.D., President and CSO at Regeneron
Ongoing Development and Future Outlook
Itepekimab is still under clinical evaluation and has not yet been approved by regulatory authorities. It is being studied in:
- CRSwNP (Chronic Rhinosinusitis with Nasal Polyps) – Phase 3
- CRSsNP (without Nasal Polyps) – Phase 2
- Non-cystic fibrosis bronchiectasis – Phase 2
- AERIFY-3: Mechanistic Phase 2 study (airway inflammation in COPD)
- AERIFY-4: Long-term safety Phase 3 study (COPD)
About Itepekimab
Itepekimab is a fully human monoclonal antibody that targets IL33, a cytokine believed to amplify inflammation in COPD—especially in former smokers.
About Sanofi and Regeneron
Sanofi is a global, AI-powered biopharma leader focused on immunology and vaccines. Regeneron is a biotechnology company known for groundbreaking biologics in serious diseases.
Together, they continue to drive innovation in respiratory medicine, including the landmark approval of Dupixent, the first biologic for COPD.
