Dupixent (dupilumab) approved in the EU as the first-ever targeted therapy for patients with COPD – Sanofi + Regeneron

The European Medicines Agency (EMA) has approved Dupixent (dupilumab) as an add-on maintenance treatment for adults with uncontrolled chronic obstructive pulmonary disease (COPD) characterized by raised blood eosinophils.

Specifically, the approval covers patients already on a combination of an inhaled corticosteroid (ICS), a long-acting beta2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), or on a combination of a LABA and a LAMA if ICS is not appropriate. The EMA is the first regulatory authority in the world to approve Dupixent for COPD patients. Additional submissions are under review with other regulatory authorities around the world, including in the US, China, and Japan.

The approval is based on results from the landmark phase III BOREAS and NOTUS studies, which were separately published in The New England Journal of Medicine (previously cited) and evaluated the efficacy and safety of Dupixent in adults with uncontrolled COPD with evidence of type 2 inflammation (i.e., blood eosinophils greater than 300 cells per uL). All patients were on background maximal standard-of-care inhaled therapy (with nearly all on triple therapy).

In terms of efficacy, Dupixent patients in BOREAS (n=468) and NOTUS (n=470) experienced the following, respectively, compared to placebo (BOREAS n=471; NOTUS n=465) : i. 30% and 34% reduction in the annualized rate of moderate or severe COPD exacerbations over 52 weeks, the primary endpoint. ii. Improvements in lung function (pre-bronchodilator FEV1) from baseline by 160 mL and 139 mL at 12 weeks compared to 77 mL and 57 mL. These improvements were observed as early as week 2 and 4 and were sustained at 52 weeks in both studies. iii. Improvements in health-related quality of life (statistically significant in BOREAS and nominally significant in NOTUS), as assessed by the St. George’s Respiratory Questionnaire. iv. Reductions in exacerbations and improvements in lung function for Dupixent versus placebo were also observed in patients with higher baseline fractional exhaled nitric oxide (greater than 20ppb) – an airway biomarker of inflammation – and across all pre-defined subgroups including smoking status, baseline lung function, and history of exacerbations.

Safety results in both studies were generally consistent with the known safety profile of Dupixent in its approved indications. The most common side effects across indications include injection site reactions, conjunctivitis, conjunctivitis allergic, arthralgia, oral herpes, and eosinophilia. Adverse events more commonly observed with Dupixent ( greater than 5%) compared to placebo in either COPD study were back pain, COVID-19, diarrhea, headache and nasopharyngitis. Additional adverse reactions of injection site bruising, injection site induration, injection site rash and injection site dermatitis were reported in the COPD studies.