Regulatory Decision Summary for Dupixent

Asthma is a heterogeneous disease characterized by chronic variable and reversible airflow obstruction, bronchial hyperresponsiveness, and chronic airway inflammation. Severe asthma affects 3-10% of asthmatics; however, this small minority of individuals are often at greatest risk of severe exacerbation and mortality.

The benefits of Dupixent as an add-on maintenance treatment in patients aged 12 years and older with severe asthma with a Type 2/eosinophilic phenotype or oral corticosteroid-dependent asthma were primarily demonstrated in a phase 3 exacerbation study (QUEST), which was supported by a phase 2b dose-ranging study (DRI12544), and a phase 3 oral corticosteroid (OCS) sparing study (VENTURE). QUEST was a 52-week randomized, double-blind, placebo-controlled, parallel-group, multi-centre study that included 1,902 subjects (12 years of age and older) with severe asthma. VENTURE was a 24-week randomized, double-blind, placebo-controlled, parallel-group, multi-centre oral corticosteroid (OCS) reduction study in 210 subjects with severe asthma receiving high-dose inhaled corticosteroids plus additional controller(s) (e.g., LABA) and OCS.

In QUEST, Dupixent resulted in a statistically significant reduction in the annualized rate of severe exacerbations and a statistically significant improvement in lung function as measured by forced expiratory volume in 1 second (FEV1) at Week 12. The improvement in lung function appeared to be maintained through 52 weeks of treatment. The beneficial effect of Dupixent on both reduction in annualized rate of severe exacerbation and improvement in FEV1 were more pronounced in subjects with higher baseline blood eosinophil levels and higher baseline fractional exhaled nitric oxide (FeNO) levels. Additionally, differences in favour of Dupixent were observed at Week 24 in the proportion of subjects experiencing a clinically meaningful change in asthma symptomology and quality of life, as measured by the Asthma Control Questionnaire (ACQ)-5 and Standardized Asthma Quality of Life Questionnaire (AQLQ(S)), respectively.

In VENTURE, Dupixent resulted in a favourable reduction in daily OCS dose from baseline at Week 24 while maintaining asthma control. A numerically greater proportion of subjects receiving Dupixent had a 50% or higher reduction in OCS dose, a complete weaning of OCS dose, and a final OCS dose less than 5 mg. In VENTURE, changes in annualized rate of severe exacerbations, FEV1, ACQ-5, and AQLQ(S) were relatively consistent with those observed in QUEST.

The safety of Dupixent in subjects with severe asthma is considered consistent with the established risk profile for Dupixent.

Overall, the benefit-risk profile for Dupixent (dupilumab injection) is considered to be positive, which supports an extension to the indication as an add-on maintenance treatment in patients aged 12 years and older with severe asthma with a Type 2/eosinophilic phenotype or oral corticosteroid-dependent asthma.