A pooled analysis of the BOREAS and NOTUS phase 3 studies demonstrates that Dupixent (dupilumab) significantly reduces exacerbations and improves lung function in adults with uncontrolled chronic obstructive pulmonary disease (COPD) and evidence of type 2 inflammation, as indicated by raised blood eosinophils. The findings, a collaboration between Sanofi and Regeneron, were presented at the 2024 European Respiratory Society (ERS) International Congress.
The analysis combined data from 1,874 patients enrolled in the BOREAS and NOTUS trials, all of whom were current or former smokers with moderate-to-severe COPD and blood eosinophil levels of ≥300 cells per μL. Patients received either Dupixent or placebo every two weeks for 52 weeks, in addition to maximal standard-of-care inhaled triple therapy (ICS, LABA, and LAMA) or double maintenance therapy (LABA and LAMA) if ICS was not appropriate.
Key Findings from the Pooled Analysis
Compared to placebo, Dupixent-treated patients (n=938) experienced a 31% reduction in the annualized rate of moderate or severe COPD exacerbations over 52 weeks (nominal p<0.0001). Furthermore, lung function, measured by pre-bronchodilator FEV1, improved by 147 mL from baseline at 12 weeks in the Dupixent group, compared to 64 mL in the placebo group (nominal p<0.0001). These improvements were observed as early as two weeks and sustained through 52 weeks (nominal p<0.0001).
Safety Profile
The safety results from the pooled analysis were consistent with the known safety profile of Dupixent in its approved indications. Overall rates of adverse events (AEs) were similar between the Dupixent (72%) and placebo (71%) groups. The most common AEs observed more frequently with Dupixent included nasopharyngitis (7.8% vs. 7.4% for placebo) and headache (7.8% vs. 6.6% for placebo). Deaths occurred in 2% of Dupixent-treated patients and 1.6% of placebo-treated patients.
Expert Commentary
Surya Bhatt, M.D., MSPH, Professor at the University of Alabama at Birmingham, US, Division of Pulmonary, Allergy, and Critical Care Medicine, and a co-principal investigator of the study, emphasized the clinical significance of these findings: "For far too long, I have watched patients with uncontrolled COPD struggle with a relentless cycle of exacerbations that diminish lung function, with no new treatment approaches to help alleviate this downward spiral. The pooled analysis of the pivotal BOREAS and NOTUS phase 3 studies provide more comprehensive examination of the unprecedented efficacy and safety data, which reinforce the benefit of dupilumab for patients on maximal inhaled therapy and limited additional options."
Regulatory Status and Future Directions
Dupixent has already received regulatory approval in the European Union, Brazil, and Russia as an add-on maintenance treatment for adults with uncontrolled COPD characterized by raised blood eosinophils. Regulatory submissions are currently under review in the US, China, Japan, and other regions.
Sanofi and Regeneron are also investigating itepekimab, a monoclonal antibody that inhibits interleukin-33 (IL33), as another potential treatment for COPD. Itepekimab is currently in phase 3 clinical trials.
About COPD
COPD is a progressive respiratory disease that damages the lungs, leading to lung function decline. It is the fourth leading cause of death worldwide. Symptoms include chronic cough, excessive mucus production, and shortness of breath, which can significantly impair daily activities. COPD exacerbations contribute to a substantial health and economic burden, often requiring systemic corticosteroid treatment and/or hospitalization.
