Dupilumab Reduces Exacerbations and Improves Lung Function and Quality of Life in Patients with Chronic Obstructive Pulmonary Disease and Type 2 Inflammation: The Notus Trial

S Bhatt; A Hoheisel; K Rabe; N Hanania; C Vogelmeier; M Bafadhel; S Christenson; A Papi; E Laws; J Maloney; X Lu; D Bauer; A Bansal; R Abdulai; L Robinson

doi:10.1055/s-0045-1804578

Pneumologie, Table of Contents

Pneumologie 2025; 79(S 01): S20
DOI: 10.1055/s-0045-1804578

Abstracts

A2 – COPD

Dupilumab Reduces Exacerbations and Improves Lung Function and Quality of Life in Patients with Chronic Obstructive Pulmonary Disease and Type 2 Inflammation: The Notus Trial

Authors

S Bhatt

¹University of Alabama at Birmingham; Division of Pulmonary, Allergy, and Critical Care Medicine
A Hoheisel

²University Medical Center Freiburg, Medical Faculty, Albert-Ludwigs-University Freiburg. Pneumological-Allergological Practice/Study Center Leipzig; Department of Pneumology
K Rabe

³Lungenclinic Grosshansdorf und Klinik für Innere Medizin, Christian-Albrechts Universität, Kiel; Zentrum Für Pneumologie Und Thoraxchirurgie; Pneumologie
N Hanania

⁴Baylor College of Medicine
C Vogelmeier

⁵Phillips-Universität Marburg; Department of Medicine, Pulmonary, and Critical Care Medicine
M Bafadhel

⁶King’s Centre for Lung Health, King’s College London
S Christenson

⁷University of California San Francisco
A Papi

⁸Respiratory Medicine Unit, University of Ferrara, S. Anna University Hospital
E Laws

⁹Sanofi
J Maloney

¹⁰Regeneron Pharmaceuticals Inc.
X Lu

⁹Sanofi
D Bauer

⁹Sanofi
A Bansal

¹⁰Regeneron Pharmaceuticals Inc.
R Abdulai

⁹Sanofi
L Robinson

⁹Sanofi

Abstract

Full Text

Introduction: Phase 3 BOREAS (NCT03930732) demonstrated efficacy and a significant reduction in exacerbation frequency in patients (pts) with chronic obstructive pulmonary disease (COPD) and type 2 inflammation. Phase 3 NOTUS (NCT04456673) aimed to confirm the efficacy and safety of dupilumab (DPL) in the same pt population as BOREAS.

Methods: NOTUS was a 52-week (w), randomized, double-blind, placebo (PBO)-controlled trial assessing efficacy and safety of subcutaneous add-on DPL 300 mg q2w or PBO. Enrolled pts (40 to 85 years) with COPD had moderate-to-severe airflow limitation, type 2 inflammation (blood eosinophils [eos]≥300 cells/μL at screening) and were on triple therapy with inhaled corticosteroids (ICS), long-acting β₂-agonists (LABA), and long-acting muscarinic antagonists (LAMA) (or LABA/LAMA if ICS were contraindicated). Primary analysis was performed on interim data.

Results: Pts (N=935) were randomized to DPL/PBO (n=470/465). DPL vs PBO reduced the annualized moderate-to-severe exacerbation rates (primary endpoint) by 34% (relative risk [95% CI] 0.664 [0.535, 0.823]; P=0.0002). At W12, DPL increased pre-bronchodilator FEV₁ (LS mean difference: 82 mL; P=0.0001) vs PBO, maintained at W52 (LS mean difference: 62 mL; P=0.0182). DPL improved St. George's Respiratory Questionnaire score at W52 (LS mean difference:−3.37; nominal P=0.0068) vs PBO. The median change in blood eos (cells/μL) from baseline (BL) to W52 was –45 for DPL vs –40 for PBO. For the BL (Week 0) blood eos subgroup analysis, reduction in annualized moderate-to-severe exacerbation rates was similar in those with BL blood eos<300 (n=372) or≥300 (n=562) cells/μL (relative risk vs PBO: 0.620 and 0.685, respectively). Safety findings were similar to BOREAS.

Conclusions: In pts with COPD and type 2 inflammation, DPL reduced rates of moderate or severe exacerbations in both patients with blood eos counts<300 and≥300 cells/μL, and improved lung function and health-related quality of life. The safety profile of DPL was generally consistent with other DPL indications.