Late-stage results from the NOTUS trial showed Sanofi and Regeneron’s Dupixent lowered moderate to severe chronic obstructive pulmonary disease exacerbations by 34% and led to significantly better lung function.
Sanofi and Regeneron Pharmaceuticals on Monday unveiled results from the Phase III NOTUS trial, demonstrating that their blockbuster monoclonal antibody Dupixent (dupilumab)—when used as an add-on maintenance treatment—can significantly reduce exacerbations in patients which chronic obstructive pulmonary disease.
The data, presented during a late-breaking session at the 2024 American Thoracic Society (ATS) International Conference, showed that Dupixent cut moderate to severe exacerbations by 34% over 52 weeks. The effect was statistically significant with a p-value less than 0.001, according to the announcement.
Dupixent also met its key secondary endpoints, more than doubling lung function at 12 weeks, an effect that persisted through 52 weeks. Patients treated with the therapeutic antibody also had better health-related quality of life and lower respiratory symptoms severity.
The safety profile for Dupixent in NOTUS was consistent with what had previously been observed in its approved indications. In the Dupixent arm, 2.6% of patients died due to adverse events compared to 1.5% in placebo. It is unclear if these fatal toxicities were associated or causally linked to Dupixent.
“In NOTUS, dupilumab reduced exacerbations by a magnitude never seen before with an investigational biologic” in chronic obstructive pulmonary disease (COPD), Surya Bhatt, co-principal investigator of the study, said in a statement. If approved, NOTUS’ data suggest that “dupilumab could provide a first-of-its-kind medical advancement for the COPD community.”
Bhatt has served as an advisor for Sanofi and Regeneron.
Monday’s readout comes as Sanofi and Regeneron are awaiting the FDA’s verdict for their application to use Dupixent in COPD. In February 2024, the regulator granted the partners’ Biologics License Application priority review, with a decision expected by June 27, 2024.
In addition to NOTUS, Dupixent’s COPD bid is supported by the Phase III BOREAS trial, which in May 2023 demonstrated that adding the biologic to maximal standard-of-care—including an inhaled triple therapy—reduced moderate or severe acute COPD exacerbations by 30% over 52 weeks.
The Dupixent regimen also improved lung function by 160 mL after 12 weeks, an effect that satisfied statistical significance. Dupixent treatment also significantly improved health-related quality of life and lowered respiratory symptom severity.
Regeneron and Sanofi are also seeking COPD approvals for Dupixent in the European Union and China.
Dupixent is a human monoclonal IgG4 antibody designed to target and block the IL-5 and IL-13 cytokines, preventing their downstream pro-inflammatory signaling cascades. This mechanism of action allows Dupixent to dampen type 2 inflammation, which is often an underlying pathological pathway in many immune diseases.
The anti-inflammatory antibody is currently approved for atopic dermatitis, eosinophilic esophagitis, prurigo nodularis, chronic rhinosinusitis with nasal polyps and asthma.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
