The European Commission has approved Dupixent ( Dupilumab ) for use in adults and adolescents 12 years and older as an addon maintenance treatment for severe asthma with type 2 inflammation characterized by raised blood eosinophils and/or raised fractional exhaled nitric oxide ( FeNO ), who are inadequately controlled with high dose inhaled corticosteroid ( ICS ) plus another medicinal product for maintenance treatment.
Despite standard-of-care treatment, people with severe asthma often have inadequately controlled, persistent symptoms that may make them suitable for treatment with a biologic therapy.
These patients live with coughing, wheezing and difficulty breathing, and are at risk of severe asthma attacks that may require emergency room visits or hospitalizations.
In addition to taking maintenance ICS treatment, patients with severe asthma often rely on oral corticosteroids ( OCS ) when their symptoms worsen.
While OCS can provide relief for severe symptoms, current asthma guidelines suggest limiting their chronic use to the most severe patients due to the potential for serious side effects.
Type 2 inflammation is responsible for many of the hallmark symptoms of asthma and Dupixent is the first and only treatment approved for patients in the European Union with severe asthma characterized by multiple biomarkers of type 2 inflammation.
Dupilumab is a human monoclonal antibody that inhibits the signaling of interleukin-4 ( IL-4 ) and interleukin-13 ( IL-13 ), two key proteins that play a central role in type 2 inflammation that underlies specific types of asthma as well as several other allergic diseases.
This effect is associated with the reduction of type 2 inflammatory biomarkers including FeNO, immunoglobulin E ( IgE ) and eotaxin-3 ( CCL26 ).
The EC approval is based on clinical data from 2,888 adults and adolescents who participated in three pivotal trials from the global LIBERTY ASTHMA program, including the phase 3 QUEST and VENTURE trials and a phase 2b trial.
QUEST enrolled 1,902 patients with persistent asthma and evaluated whether adding Dupilumab to standard-ofcare therapy could reduce severe exacerbations and improve lung function ( measured by FEV1 ).
VENTURE enrolled 210 patients with severe oral corticosteroid-dependent asthma and evaluated whether adding Dupilumab to standard-of-care therapy could reduce the use of maintenance oral corticosteroids.
The phase 2b trial enrolled 776 adult patients with moderate-to-severe asthma and evaluated whether adding Dupilumab to standard-of-care therapy could improve lung function.
In these trials, Dupilumab:
Reduced severe exacerbations: In QUEST, by week 52 exacerbations were reduced by up to 67% compared to placebo in patients with eosinophils greater than or equal to 300 cells/microliter and up to 65% for those with FeNO levels greater than or equal to 25 parts per billion. In the phase 2b trial, by week 24 exacerbations were reduced by up to 81% compared to placebo in patients with eosinophils greater than or equal to 300 cells/microliter.
Improved lung function: In QUEST, by week 12 Dupilumab improved FEV1 by up to 33% ( vs. up to 16% for placebo ) in patients with blood eosinophils of greater than or equal to 300 cells/microliter and up to 30% ( vs. up to 14% for placebo ) in patients with FeNO greater than or equal to 25 parts per billion. In the phase 2b trial, by week 12 Dupilumab improved FEV1 by up to 26% ( vs. 10% for placebo ) in patients with blood eosinophils of greater than or equal to 300 cells/microliter.
Reduced oral corticosteroid use: In VENTURE, by week 24 more than half of Dupilumab patients completely eliminated oral corticosteroids, and overall use reduced by 70% ( vs. 42% for placebo ).
Safety: In asthma clinical trials, the most common adverse reaction was injection site erythema. Anaphylactic reaction has been reported very rarely in the asthma development program.
All trials enrolled patients irrespective of minimum baseline type 2 inflammatory biomarkers, such as eosinophils or FeNO levels.
Updated Global Initiative for Asthma ( GINA ) guidelines characterize type 2 inflammation by eosinophils greater than or equal to 150 cells/microliter or FeNO greater than or equal to 20 parts per billion.
In these pivotal trials, patients with eosinophils greater than or equal to 150 cells/microliter or FeNO greater than or equal to 25 parts per billion benefited most from Dupilumab.
In the phase 2b trial and QUEST, the greatest improvements in exacerbations and lung function were observed in patients with higher baseline levels of type 2 disease.
In VENTURE the effect of Dupilumab on oral corticosteroid use, exacerbations and lung function, was similar irrespective of baseline levels of type 2 inflammation. ( Xagena )
Source: Sanofi, 2019