Date: 2013-05-21
Type of
information: Results
phase: 2a
Announcement: results
Company: Sanofi (France) Regeneron Pharmaceuticals (USA)
Product: dupilumab
Action
mechanism:
- monoclonal antibody. Dupilumab (SAR231893/REGN668) is a fully human monoclonal antibody directed against IL-4R alpha and is administered via subcutaneous injection. By blocking IL-4R alpha dupilumab modulates signaling of both IL-4 and IL-13, drivers of a Th2 immune response. Dupilumab was created using Regeneron's VelocImmune® technology and is being co-developed with Sanofi.
- Atopic dermatitis and some types of asthma are characterized by the induction of a specific type of an immune response that is driven by a subset of immune cells called Type 2 helper T cells, or Th2 cells. IL-4 and IL-13 are key cytokines that are required for the initiation and maintenance of this Th2 immune response. IL-4 and IL-13 signaling occurs through Type I and II IL-4 receptors (IL-4 through both receptors and IL-13 through Type II receptors), which both contain a common IL-4R alpha subunit.
Disease: asthma
Therapeutic
area: Respiratory diseases - Inflammatory diseases - Allergic diseases
Country:
Trial
details:
- The proof-of-concept study enrolled 104 patients with moderate-to-severe, persistent asthma that was not well controlled with inhaled glucocorticosteroids (ICS) and long-acting beta agonist (LABA) therapy, and who had elevated blood or sputum eosinophils (immune cells used as a marker of Th2 asthma in this study).
- The primary objective of the trial was to assess the effect of dupilumab, dosed subcutaneously, weekly at 300 milligrams (mg) for twelve weeks. Patients were treated with dupilumab (N=52) or placebo (N=52) on top of ICS and LABA therapy for the first four weeks of the study. The LABA was withdrawn at week four and the ICS was tapered to withdrawal between weeks six and nine. Patients were treated for 12 weeks or until they experienced a protocol-defined asthma exacerbation, the primary endpoint of the study. 23 patients (44.2%) receiving placebo experienced an asthma exacerbation compared to three patients (5.8%) receiving dupilumab, resulting in an 87% reduction in the incidence of asthma exacerbations for the dupilumab arm compared to placebo (p < 0.0001).
- Clinically meaningful and statistically significant improvements were observed for lung function and other asthma control parameters, such as forced expiratory volume over one second (FEV1) (difference from baseline to week 12 between dupilumab and placebo of 0.27 L, p < 0.001).
Latest
news:
- • On May 21, 2013, Sanofi and Regeneron Pharmaceuticals have announced that the New England Journal of Medicine published online the positive Phase 2a study results of dupilumab (SAR231893/REGN668) in patients with moderate-to-severe allergic asthma. The study results will also be presented at a late-breaking clinical trials session at the American Thoracic Society 2013 International Conference.
- Patients were treated with dupilumab (N=52) or placebo (N=52) on top of ICS and LABA therapy for the first four weeks of the study. The LABA was withdrawn at week four and the ICS was tapered to withdrawal between weeks six and nine. Patients were treated for 12 weeks or until they experienced a protocol-defined asthma exacerbation, the primary endpoint of the study. 23 patients (44.2%) receiving placebo experienced an asthma exacerbation compared to three patients (5.8%) receiving dupilumab, resulting in an 87% reduction in the incidence of asthma exacerbations for the dupilumab arm compared to placebo.
- Clinically meaningful and statistically significant improvements were observed for lung function and other asthma control parameters, such as forced expiratory volume over one second (FEV1) (difference from baseline to week 12 between dupilumab and placebo of 0.27 L).
- Treatment-emergent adverse events (AEs) were reported by a similar proportion of patients in both groups (76.9% placebo; 80.8% dupilumab). AEs were generally non-specific and of mild-to-moderate intensity. The most common AEs for placebo and dupilumab were injection-site reaction (9.6% and 28.8%), nasopharyngitis (3.8% and 13.5%), upper respiratory tract infection (17.3% and 13.5%), headache (5.8% and 11.5%) and nausea (1.9% and 7.7%).
Is
general: Yes
