Dupixent phase III COPD results presented at ATS meeting and simultanously published in NEJM

The Dupixent Phase III results were presented in the 2023 American Thoracic Society (ATS) International Conference session “New England Journal of Medicine and JAMA. Discussion on the Edge: Reports of Recently Published Pulmonary Research” and simultaneously published in the New England Journal of Medicine (NEJM). These results will also be presented in the “Breaking News: Clinical Trial Results in Pulmonary Medicine” session on May 22.

“I've seen patients with uncontrolled chronic obstructive pulmonary disease struggle for far too long with the debilitating symptoms of this progressive disease – with limited, incremental improvement on current treatment options,” said Surya Bhatt, M.D., MSPH, Associate Professor at the University of Alabama at Birmingham Division of Pulmonary, Allergy, and Critical Care Medicine, and a co-principal investigator of the trial. “This trial showed that dupilumab has the potential to impact the vicious cycle of exacerbations and lung function decline in patients with uncontrolled COPD with type 2 inflammation, and significantly improve respiratory symptoms. Dupilumab also helped improve health-related quality of life measures, which, from my years of experience as a physician, are just as meaningful for patients as being able to breathe easier.”

The results presented at ATS and published in NEJM are from the BOREAS trial, which met the primary and all key secondary endpoints. As presented and published, patients receiving Dupixent (n=468) compared to placebo (n=471) added to maximal standard-of-care inhaled triple therapy experienced a: i.30% reduction in moderate or severe acute COPD exacerbations over 52 weeks (p<0.001), the primary endpoint. ii. 160 ml improvement in lung function from baseline at 12 weeks versus 77 ml (p><0.001). iii. numerical improvements were observed as early as 2 weeks, with the benefit versus placebo sustained through 52 weeks (dupixent: 153 ml, placebo: 70 ml; p><0.001). iv. 9.7-point improvement in health-related quality of life (qol; patient-reported outcome on a scale from 0-100) from baseline at 52 weeks versus a 6.4-point improvement (p="0.002)," with numerical improvements observed as early as 4 weeks. v. 2.7-point reduction in respiratory symptom severity (patient-reported outcome on a scale from 0-40) from baseline at 52 weeks versus a 1.6-point reduction (p="0.001)."

In a pre-specified analysis from a subgroup of patients (Dupixent n=195, placebo n=188) with elevated levels ( greater than 20 ppb) of fractional exhaled nitric oxide (FeNO) – an airway biomarker of type 2 inflammation – Dupixent treatment also led to a significant 38% reduction in exacerbations compared to placebo at 52 weeks (p=0.005). In this subgroup, Dupixent also led to an improvement in lung function of 232 mL versus 108 mL for placebo at 12 weeks (p=0.002) that was sustained at 52 weeks with an improvement in lung function of 247 mL versus 120 mL for placebo (p=0.003).

The safety results were generally consistent with the known safety profile of Dupixent in its approved indications. Overall rates of adverse events (AEs) were 77% for Dupixent and 76% for placebo. AEs more commonly observed with Dupixent compared to placebo included headache (8.1% Dupixent, 6.8% placebo), diarrhea (5.3% Dupixent, 3.6% placebo) and back pain (5.1% Dupixent, 3.4% placebo). AEs more commonly observed with placebo compared to Dupixent included upper respiratory tract infection (9.8% placebo, 7.9% Dupixent), hypertension (6.0% placebo, 3.6% Dupixent) and COVID-19 (5.7% placebo, 4.1% Dupixent). AEs leading to deaths were balanced between the two arms (1.7% placebo, 1.5% Dupixent).

The second, replicate Phase III trial of Dupixent in COPD with evidence of type 2 inflammation (NOTUS) is ongoing, with data expected in 2024. The safety and efficacy of Dupixent in COPD are currently under clinical investigation and have not been evaluated by any regulatory authority. Regeneron and Sanofi look forward to discussing the BOREAS data with regulators.

About the Dupixent COPD Phase III Trial Program: BOREAS is one of two pivotal trials in the Dupixent COPD program. The randomized, Phase III, double-blind, placebo-controlled trial evaluated the efficacy and safety of Dupixent in 939 adults who were current or former smokers aged 40 to 80 years with moderate-to-severe COPD. All patients in the trial had evidence of type 2 inflammation, as measured by blood eosinophils greater than 300 cells/µL. Patients with a diagnosis or history of asthma were excluded from the trial. During the 52-week treatment period, patients 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 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 and other hierarchy endpoints included: i. Change from baseline in lung function (assessed by pre-bronchodilator forced expiratory volume over one second [FEV1]) at 12 and 52 weeks in both the overall population and those with FeNO greater than 20 ppb. ii. Change from baseline at 52 weeks in St. George’s Respiratory Questionnaire (SGRQ) total score compared to placebo (scale from 0-100). iii. Change from baseline at 52 weeks in the Evaluating Respiratory Symptoms in COPD (E-RS: COPD) scale score (scale from 0-40). iv. The annualized rate of acute moderate or severe COPD exacerbations in patients with FeNO greater than 20 ppb.

See- "Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts"- Surya P. Bhatt, M.D., M.S.P.H., Klaus F. Rabe, M.D., Ph.D., Nicola A. Hanania, M.D., Claus F. Vogelmeier, M.D, et al., May 21, 2023 DOI: 10.1056/NEJMoa2303951.