Regeneron and Sanofi’s Dupilumab is the first biologic to demonstrate a clinically meaningful and statistically significant reduction in exacerbations compared with the placebo.
The primary and all key secondary endpoints were met in a phase 3 trial evaluating the investigational use of dupilumab (Dupixent) from Regeneron Pharmaceuticals Inc and Sanofi compared with the placebo in adults on the maximal standard-of-care inhaled therapy with uncontrolled chronic obstructive pulmonary disease (COPD) and evidence of type 2 inflammation.
Dupilumab is a fully human monoclonal antibody that inhibits the signaling of the interleukin (IL)-4 and IL-13 pathways and is not an immunosuppressant.
“COPD is an urgent global health concern and a notoriously difficult-to-treat disease, due to its heterogeneity, with no novel treatments approved in more than a decade,” George Yancopoulos, MD, PhD, chief scientific officer and president of Regeneron, said in a statement.
“In this landmark phase 3 trial, patients with uncontrolled COPD achieved clinical outcomes with [dupilumab] at a magnitude never before seen with a biologic,” he said. “These results also validate the role type 2 inflammation plays in driving COPD in these patients, advancing the scientific community’s understanding of the underlying biology of this disease.”
Dupilumab is the first biologic to demonstrate a clinically meaningful and highly significant reduction of 30% in moderate or severe acute exacerbation of COPD, with acute and rapid worsening of respiratory symptoms over 52 weeks, while demonstrating significant improvements in COPD respiratory symptoms, lung function, and quality of life.
In the BOREAS (NCT03662126) trial, which is the first of 2 phase 3 trials, investigators enrolled 939 individuals aged 40 to 80 years who smoke or used to smoke. Individuals were randomized to receive dupilumab or the placebo added to the maximal standard-of-care inhaled therapy.
Investigators found that there was a 30% reduction in moderate-to-severe acute COPD exacerbations over 52 weeks, which was the primary endpoint.
Additionally, they found improved lung function from the baseline by 160 mL at 12 weeks compared with 77 mL for the placebo, with the benefit sustained through week 52 compared with the placebo. These were both the key secondary endpoints.
Furthermore, dupilumab met all endpoints that were tested in the hierarchy, which included improvement in patient-reported health-related quality of life as measured by the St. George’s Respiratory Questionnaire and reduction in the severity of respiratory symptoms of COPD, measured by the Evaluation Respiratory Symptoms: COPD Scale.
Investigators reported that the safety results were generally consistent with the known safety profile of dupilumab in the approved indications.
The overall rates of adverse events (AEs) were 77% for dupilumab and 76% for the placebo. The AEs more commonly observed with dupilumab compared with the placebo included back pain, diarrhea, and headaches.
Additionally, the AEs leading to deaths were comparable in the 2 arms at 1.7% for the placebo and 1.5% for dupilumab.
Detailed efficacy and safety results will be presented in a future scientific forum, according to the statement from Regeneron.
Dupilumab has received regulatory approvals in 1 or more countries around the world for individuals with asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis.
Dupixent (dupilumab) demonstrates potential to become first biologic to treat COPD by showing significant reduction in exacerbations in pivotal trial. Regeneron Pharmaceuticals. News release. March 23, 2023. Accessed March 24, 2023. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-demonstrates-potential-become-first-biologic