DUPIXENT (dupilumab) - Chronic obstructive pulmonary disease (COPD)

The Committee deems that the clinical benefit of DUPIXENT (dupilumab) is moderate in adults as add-on maintenance treatment for uncontrolled chronic obstructive pulmonary disease (COPD) characterised by raised blood eosinophils 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.

Considering:

• evidence of the superiority of DUPIXENT (dupilumab) compared to placebo, as add-on therapy to maintenance treatment with ICS/LABA/LAMA or LABA/LAMA if ICS is contraindicated, in two randomised, double-blind studies, for the annualised rate of moderate or severe exacerbations of COPD at 52 weeks, a clinically relevant endpoint;
• a modest effect size, with a risk reduction of 30% (RR=0.70; 95% CI: [0.58; 0.86], p=0.0005) in the BOREAS study and 34% (RR=0.66; 95% CI: [0.53; 0.82], p=0.0002) in the NOTUS study compared to maintenance treatment alone;
• on respiratory function at 52 weeks, with a pre-BD FEV₁ of +83 mL (95% CI: [38; 128], p < 0.0001) in the BOREAS study and +62 mL (95% CI: [11; 113], p=0.0182) in the NOTUS study compared to maintenance therapy alone;
• the improvement in quality of life at 52 weeks (assessed using the SGRQ score, concerning the change in total SGRQ score and the percentage of patients with a reduction in SGRQ score ≥ 4 points ) in the BOREAS study compared to maintenance therapy alone;
• its acceptable safety profile;
• the unmet medical need in patients with COPD that is not controlled by an ICS/LABA/LAMA combination or a LABA/LAMA combination;

but in view of:

• the number of patients in the placebo group with no exacerbations during the study, reflecting control of the disease with the background therapy;
• the low annualised rate of exacerbations during the study in patients on placebo (1.1 to 1.3);
• an efficacy assessed on the basis of moderate and severe exacerbations, with no effect measured on each component of this endpoint, which nonetheless each have a different significance for patients (depending on whether they are moderate or severe, exacerbations have different impacts in terms of symptoms, quality of life and hospitalisations);
• with the effect appearing to primarily involve moderate exacerbations (90% of the exacerbations observed);
• smoking cessation and respiratory rehabilitation implemented in a non-optimal manner;
• the absence of available data concerning the course of COPD, in particular for the annualised rate of exacerbations, beyond one year of treatment;
• the lack of evidence of any impact on quality of life in one study;

the Committee deems that DUPIXENT (dupilumab) provides a minor clinical added value (CAV IV) in the care pathway for the treatment of uncontrolled COPD characterised by raised blood eosinophils on a combination of ICS/LABA/LAMA, or on a combination of a LABA/LAMA if ICS is not appropriate.