Regeneron Pharmaceuticals and Sanofi announced the Phase 3 investigational study evaluating dupilumab in adults and adolescents with severe, steroid-dependent asthma met its primary endpoint and key secondary endpoints. 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 percent on average (median reduction of 100 percent) compared to 42 percent with placebo (median reduction of 50 percent) (p less than 0.0001). In prespecified analyses of patients with baseline eosinophil counts greater than or equal to 300 cells/microliter, adding dupilumab significantly reduced OCS use by 80 percent on average (median reduction of 100 percent) compared to 43 percent for placebo (median reduction of 50 percent) (nominal p equals 0.0001).
At 24 weeks, despite the reduced use of OCS, patients treated with dupilumab had 59 percent fewer attacks (exacerbations) in the overall population (p less than 0.0001) and 71 percent fewer attacks in patients with eosinophil counts greater than or equal to 300 cells/microliter. Also at 24 weeks, compared to placebo, dupilumab improved lung function, as assessed by forced expiratory volume over one second (FEV1) by 220ml (15 percent) in the overall population (p equals 0.0007) and by 320ml (25 percent) in patients with eosinophil counts greater than or equal to 300 cells/microliter (nominal p equals 0.0049).
"This Phase 3 study showed that most severe asthma patients could substantially reduce their dependence on oral corticosteroids, with half completely eliminating their use of oral corticosteroids, which are not recommended for long-term use and can carry significant and potentially irreversible safety risks. Importantly, despite a reduction in oral corticosteroid use, dupilumab was associated with an improvement in lung function. This is the third study in which dupilumab has demonstrated a reduction in asthma attacks and improvement in lung function in a broad group of patients with uncontrolled asthma – this effect was most profound in patients with elevated markers of Type 2 allergic inflammation, such as an eosinophil count over 300," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron. "Dupilumab blocks the IL-4/IL-13 pathway, which is emerging as a central driver of Type 2 allergic inflammation. We remain committed to investigating dupilumab in other Type 2 inflammatory diseases including eosinophilic esophagitis, nasal polyps, pediatric atopic dermatitis and food allergy."
The safety and tolerability profile of dupilumab in this study was consistent with previous studies. There were more dupilumab-treated patients with injection site reactions (9 percent dupilumab vs. 4 percent placebo). There were more dupilumab-treated patients with an increase in eosinophil counts (14 percent dupilumab vs. 1 percent 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.
Patients with severe chronic asthma live with a profound decrease in their lung function, approximately 52 percent of predicted normal for those in this study at baseline, which impacts their ability to breathe normally, and may lead to frequent exacerbations that require acute treatment and hospitalization. These problems occur even in patients who are treated with chronic OCS to manage their symptoms.