Two Phase 3 trials for the investigational use of Sanofi’s Dupixent (dupilumab) in moderate-to-severe asthma showed that the drug significantly reduced the risk of severe asthma attacks (exacerbations), improved lung function, and reduced dependence on oral corticosteroids (OCS). The detailed findings were published in the New England Journal of Medicine (NEJM).
The trials, known as QUEST and VENTURE, are part of the pivotal clinical trial program that evaluated Dupixent in uncontrolled asthma patients. These data were simultaneously presented at the American Thoracic Society 2018 International Conference taking place in San Diego.
Dupixent demonstrated significant improvements in the key primary and secondary endpoints across the overall populations in both QUEST and VENTURE, with the largest benefit experienced in patients with more severe Type 2 inflammatory asthma, as evidenced by elevated blood eosinophils or exhaled nitric oxide levels.
Type 2 asthma can also be characterized by other parameters, including elevated Immunoglobulin E (IgE). Dupixent blocks the IL-4/IL-13 pathway, which is emerging as a central driver of Type 2 allergic inflammation in asthma, as well as in a range of other allergic or atopic diseases.
The Phase 3 QUEST trial showed that a broad population of adults and adolescents with moderate-to-severe asthma (no minimum blood eosinophil level requirement or other biomarker requirement at baseline) benefited when Dupixent was added to their standard therapies.
Dupixent reduced severe asthma attacks and improved lung function compared to placebo. Lung function improvements were observed from the first measurement two weeks after receiving the first dose of Dupixent, and improvements were sustained throughout the 52-week trial. Patients also reported improved asthma control and quality of life, as measured by the 5-item Asthma Control Questionnaire (ACQ-5) and Asthma Quality of Life Questionnaire (AQLQ).
The Phase 3 VENTURE study showed that adults and adolescents with severe, steroid-dependent asthma who were treated with Dupixent, when added to standard therapies, could reduce their use of OCS medications while improving asthma control compared to placebo at 24 weeks.
With Dupixent, OCS use decreased by 70 percent in the overall population (vs. 42 percent for placebo), and 80 percent for patients with baseline eosinophil levels 300 cells/microliter or greater (vs. 43 percent for placebo). Despite reductions in OCS, patients treated with Dupixent reduced the risk of severe asthma attacks and improved their lung function.
Asthma affects people of all ages. More than 22 million people in the Unitd States are known to have asthma, including nearly 6 million children, according to the National Heart, Lung, and Blood Institute.
Young children who often wheeze and have respiratory infections—as well as certain other risk factors—are at highest risk of developing asthma that continues beyond 6 years of age. The other risk factors include having allergies, eczema (an allergic skin condition), or parents who have asthma.
Among children, more boys have asthma than girls. But among adults, more women have the disease than men. It’s not clear whether or how sex and sex hormones play a role in causing asthma.
The investigational use of Dupixent as an add-on maintenance treatment of adults and adolescents with uncontrolled moderate-to-severe asthma is currently under regulatory review in several countries, including the U.S., Japan, and in the European Union (EU), and the safety and efficacy for this use have not been evaluated by any regulatory authority.
In the U.S., the target action date is October 20, 2018. Dupixent is currently approved in a number of countries for the treatment of adults with uncontrolled moderate-to-severe atopic dermatitis.
Filed Under: Drug Discovery