Sanofi and Regeneron Pharmaceuticals have reported positive results from the interim analysis of a dose-ranging Phase IIb trial of dupilumab, a fully-human monoclonal antibody, in adult patients with uncontrolled moderate-to-severe asthma.
Dupilumab is directed against the IL-4 receptor alpha subunit, which blocks signalling from both IL-4 and IL-13, which are major cytokines required for the initiation and maintenance of the Type 2 helper T-cell (Th2) immune response.
Created using Regeneron’s VelocImmune technology, dupilumab is currently being co-developed with Sanofi in asthma, atopic dermatitis and chronic sinusitis with nasal polyposis.
Sanofi Global R&D president Elias Zerhouni said: "Many have thought that targeting the Th2 pathway in asthma would limit benefit to a subset of asthmatics, such as those with high eosinophils.
"In this study, blocking IL-4/IL-13 signalling with dupilumab improved lung function and reduced severe exacerbations in the broader study population."
A total of 776 adult patients with moderate-to-severe uncontrolled asthma, were enrolled in the double-blind, placebo-controlled, 24-week, dose-ranging trial.
During the trial, patients were randomised to receive one of four doses of dupilumab (300mg every other week, 200mg every other week, 300mg monthly, 200mg monthly) or placebo.
In the Phase IIb trial, the three highest doses of dupilumab in combination with standard-of-care therapy met the primary endpoint of a statistically significant improvement from baseline in forced expiratory volume over one second at week 12 in patients with high blood eosinophils, as compared to placebo in combination with standard-of-care therapy.
Additionally, the two highest doses of dupilumab showed a statistically significant improvement in mean percent change in FEV1, as well as a reduction in severe exacerbations, in both the high eosinophils and overall trial population.
Zerhouni said: "Based on these results, we plan to move dupilumab into Phase III clinical development in patients with moderate-to-severe uncontrolled asthma."
Dupilumab is currently under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority.
Image: Obstruction of the lumen of a bronchiole by mucoid exudate, goblet cell metaplasia, and epithelial basement membrane thickening in a person with asthma. Photo: courtesy of Yale Rosen.