• Regeneron and Sanofi are actively advancing the clinical exploration of Dupilumab (DUPIXENT), a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation.
• The NOTUS study’s groundbreaking reduction in chronic obstructive pulmonary disease (COPD) exacerbations with dupilumab suggests a revolutionary advancement for the COPD patient population, potentially transforming their quality of life.

At the American Thoracic Society (ATS) 2024 International Conference, Regeneron and Sanofi presented analysis of the Phase III randomized NOTUS trial (NCT04456673) evaluating the investigational use of DUPIXENT (dupilumab) as an add-on maintenance treatment in adults with uncontrolled COPD on maximal standard-of-care inhaled therapy (nearly all on triple therapy) and evidence of type 2 inflammation (i.e., blood eosinophils ≥300 cells per μL). In Phase III, a double-blind, randomized trial, patients with COPD and blood eosinophil counts of 300 cells per microliter or higher were assigned to receive subcutaneous (SC) dupilumab (300 mg) or placebo every 2 weeks. The primary endpoint was the annualized rate of moderate or severe exacerbations. Key secondary endpoints, analyzed hierarchically to account for multiplicity, included changes from baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) at Weeks 12 and 52, as well as the St. George’s Respiratory Questionnaire (SGRQ) total score at Week 52 (with scores ranging from 0 to 100, and lower scores indicating a better quality of life.

This trial aimed to address the pressing need for more effective COPD treatments by exploring dupilumab’s potential to reduce exacerbation rates and improve lung function and quality of life. The hierarchical analysis of secondary endpoints ensures a rigorous assessment of the drug’s impact, potentially offering a breakthrough in COPD management for patients with elevated eosinophil counts.

The NOTUS study achieved its primary and key secondary endpoints, showcasing the remarkable efficacy of DUPIXENT in COPD patients already on maximal standard-of-care inhaled therapy, with nearly all participants on triple therapy. In a cohort of 470 patients treated with DUPIXENT compared to 465 on placebo, the results were compelling.

DUPIXENT led to a 34% reduction in moderate or severe COPD exacerbations over 52 weeks, underscoring its potential to alleviate the frequency of these debilitating episodes significantly. Additionally, the improvement in lung function, as measured by pre-bronchodilator FEV1, was more than twice as great with DUPIXENT compared to placebo at 12 weeks, and this improvement was sustained at 52 weeks.

Patients reported numerically greater enhancements in health-related quality of life at 52 weeks, as captured by the SGRQ. This improvement, though not statistically significant, highlights the potential for DUPIXENT to make a meaningful difference in daily living for those with COPD. Furthermore, patients experienced numerically greater reductions in respiratory symptom severity from baseline to 52 weeks, evaluated through the Evaluating Respiratory Symptoms in COPD (E-RS) tool, reinforcing the broad-spectrum benefits of DUPIXENT.

The safety profile of DUPIXENT was consistent with its established record in other approved indications. Overall, adverse event rates were similar between DUPIXENT (67%) and placebo (66%). 

DUPIXENT is currently under Priority Review by the US Food and Drug Administration (FDA) as an add-on maintenance treatment for specific adult patients with uncontrolled COPD who exhibit evidence of type 2 inflammation. The anticipated action date for this review is June 27, 2024. Concurrently, regulatory submissions are being evaluated in the European Union, and discussions with regulatory authorities worldwide are actively progressing. The global regulatory efforts reflect the widespread recognition of DUPIXENT’s promise, highlighting its potential to set a new standard of care for COPD patients who struggle with the limitations of current treatments.

In conclusion, the findings from the NOTUS study underscore the profound impact DUPIXENT could have in managing COPD. By significantly improving lung function, reducing exacerbations, and potentially enhancing the quality of life, DUPIXENT presents a promising therapeutic advancement in the fight against this chronic and challenging disease. The upcoming FDA decision, along with the ongoing evaluations in the EU and other regions, marks a pivotal moment in the advancement of COPD treatment, offering hope for enhanced quality of life and better health outcomes for patients worldwide.