A phase 3 investigational study evaluating dupilumab (Dupixent, Sanofi and Regeneron Pharmaceuticals) in adults and adolescents with severe, steroid-dependent asthma has met its primary endpoint and key secondary endpoints. Dupilumab, a fully human monoclonal antibody, was approved by the FDA in March 2017 for the treatment of adults with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies.
For the primary endpoint, at 24 weeks in the overall population, dupilumab added to standard therapies significantly reduced the use of maintenance oral corticosteroids (OCS) by 70% on average (median reduction, 100%) compared with 42% for placebo (median reduction, 50%) (P < 0.0001). In prespecified analyses of patients with baseline eosinophil counts greater than or equal to 300 cells/mcL, adding dupilumab significantly reduced OCS use by 80% on average (median reduction, 100%) compared with 43% for placebo (median reduction, 50%) (nominal P = 0.0001).
At 24 weeks, despite the reduced use of OCS, patients treated with dupilumab had 59% fewer exacerbations in the overall population (P < 0.0001) and 71% fewer attacks in patients with eosinophil counts greater than or equal to 300 cells/mcL. Also at 24 weeks, compared with placebo, dupilumab improved lung function, as assessed by forced expiratory volume over one second (FEV1) by 220 mL (15%) in the overall population (P = 0.0007) and by 320 mL (25%) in patients with eosinophil counts greater than or equal to 300 cells/mcL (nominal P = 0.0049).
The safety and tolerability profile of dupilumab in this study were consistent with previous studies. There were more dupilumab-treated patients with injection-site reactions (9% dupilumab versus 4% placebo). There were also more dupilumab-treated patients with an increase in eosinophil counts (14% dupilumab versus 1% placebo), most of which were mild and the vast majority of which resolved. The overall rates of adverse events, including infections, conjunctivitis, and herpes, were comparable between the dupilumab and placebo groups.
“Severe, uncontrolled asthma can lead to a dependence on oral corticosteroids, with systemic steroid exposure potentially leading to serious short- and long-term adverse effects, including weight gain, diabetes, osteoporosis, glaucoma, anxiety, depression, cardiovascular disease, and immunosuppression,” Mario Castro, MD, MPH, FCCP, Washington University School of Medicine in St. Louis, said in a press release. “There is an urgent need for new therapies that can decrease or eliminate chronic oral corticosteroid use, as well as reduce severe asthma attacks and improve lung function, in this difficult-to-treat patient population.”
Sanofi and Regeneron Pharmaceuticals plan to submit a supplemental biologics license application to the FDA by the end of this year.
Source: Regeneron; October 31, 2017.