Dupixent (dupilumab) late breaking data from NOTUS confirmatory phase III trial for uncontrolled COPD is presented at ATS and published in NEJM

The NOTUS trial confirmed the positive results demonstrated in the landmark Phase III BOREAS trial, with its data presented at a late-breaking session of the 2024 American Thoracic Society (ATS) International Conference and simultaneously published in the New England Journal of Medicine (NEJM).

“In my more than 20 years of practice, there have been limited advancements for patients struggling with the debilitating effects of uncontrolled COPD, and too many patients experience a vicious cycle of exacerbations that can result in loss of lung function and greatly diminish their quality of life,” said Surya Bhatt, M.D., MSPH, Professor at the University of Alabama at Birmingham, Division of Pulmonary, Allergy, and Critical Care Medicine and a co-principal investigator of the trial. “In NOTUS, dupilumab reduced exacerbations by a magnitude never seen before with an investigational biologic in a Phase 3 COPD clinical trial. These comprehensive results reinforce that, if approved, dupilumab could provide a first-of-its-kind medical advancement for the COPD community.”

As presented and published, the NOTUS trial met its primary and key secondary endpoints. All patients were on background maximal standard-of-care inhaled therapy (nearly all on triple therapy). Patients receiving Dupixent (n=470) experienced the following, compared to placebo (n=465): i. 34% reduction in moderate or severe COPD exacerbations over 52 weeks (p<0.001), the primary endpoint. ii. more than two times greater improvement in lung function (pre-bronchodilator fev1) from baseline at 12 weeks (139 ml vs. 57 ml; p><0.001), with an improvement maintained at week 52 (115 ml vs. 54 ml; p="0.018)," secondary endpoints. iii. numerically greater improvements in health-related quality of life from baseline at 52 weeks, a secondary endpoint, as defined by patient-reported outcomes (pro) in the st. george’s respiratory questionnaire (sgrq). iv. numerically greater reductions in respiratory symptom severity from baseline to 52 weeks, a secondary endpoint, as defined by pros in evaluating respiratory symptoms in copd (e-rs).

The safety results were generally consistent with the known safety profile of Dupixent in its approved indications. Overall rates of adverse events (AE) were 67% for Dupixent and 66% for placebo. AEs more commonly observed with Dupixent than placebo included COVID-19 (9.4% Dupixent, 8.2% placebo), nasopharyngitis (6.2% Dupixent, 5.2% placebo), and headache (7.5% Dupixent, 6.5% placebo). AEs more commonly observed with placebo than Dupixent included COPD (7.8% placebo, 4.9% Dupixent). AEs leading to deaths were 2.6% for Dupixent and 1.5% for placebo.

Dupixent is currently under Priority Review by the FDA as an add-on maintenance treatment in certain adult patients with uncontrolled COPD with evidence of type 2 inflammation. The target action date is June 27, 2024. Regulatory submissions are also under review in the European Union and China, and discussions with other regulatory authorities around the world are ongoing.

About the Dupixent COPD Phase III Trial Program: BOREAS and NOTUS are replicate, randomized, Phase III, double-blind, placebo-controlled trials that evaluated the efficacy and safety of Dupixent in adults who were current or former smokers with moderate-to-severe COPD. Patients were aged 40 to 80 years in BOREAS and 40 to 85 years in NOTUS. All 1,874 patients enrolled in BOREAS and NOTUS had evidence of type 2 inflammation, as measured by blood eosinophils ?300 cells per µL. Patients with a diagnosis or history of asthma were excluded from the trials. During the 52-week treatment period, patients in BOREAS and NOTUS received Dupixent or placebo every two weeks added to a maximal standard-of-care inhaled triple therapy of inhaled corticosteroids (ICS), long-acting beta agonists (LABA), and long-acting muscarinic antagonists (LAMA). Double maintenance therapy, which included LABA and LAMA, was allowed if ICS was contraindicated.

The primary endpoint for BOREAS and NOTUS evaluated the annualized rate of acute moderate or severe COPD exacerbations. Moderate exacerbations were defined as those requiring systemic steroids and/or antibiotics. Severe exacerbations were defined as those requiring hospitalization; requiring more than a day of observation in an emergency department or urgent care facility; or resulting in death. Key secondary endpoints included change from baseline in lung function (assessed by pre-bronchodilator forced expiratory volume [FEV1]) at 12 and 52 weeks, change from baseline at 52 weeks in SGRQ total score compared to placebo, and safety.