Sanofi and Regeneron Announce Publication of Positive Phase 2a Results of Dupilumab in Asthma in the New England Journal of Medicine
Phase 2a study of the IL-4R alpha inhibitor, dupilumab, demonstrated 87% reduction in risk of asthma exacerbations in moderate-to-severe asthma patients with elevated eosinophils
PARIS and TARRYTOWN, N.Y., May 21, 2013 /PRNewswire/ — Sanofi (EURONEXT: SAN and NYSE: SNY) and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today 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. Dupilumab is an investigational monoclonal antibody targeting the alpha subunit of the interleukin 4 receptor (IL-4R alpha), which modulates signaling of both IL-4 and IL-13, drivers of Th2 (Type 2 helper T cell) immune response. The study results will also be presented today at a late-breaking clinical trials session at the American Thoracic Society 2013 International Conference.
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 The LABA was withdrawn at week four and the ICS was tapered to withdrawal between weeks six and nine.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 (FEV(1)) (difference from baseline to week 12 between dupilumab and placebo of 0.27 L, p<0.001).
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%).
“Despite existing therapies, a significant number of patients with moderate-to-severe, persistent allergic asthma are not optimally controlled, which puts them at risk of poor clinical outcomes. These patients contribute to the significant economic burden of asthma,” said Sally Wenzel, M.D., Professor of Medicine and Director of the Asthma Institute at the University of Pittsburgh and lead investigator of this trial. “These encouraging data support the potential role of IL-4/IL-13 blockade in an important subset of asthma patients and warrant continued clinical investigation.”
“Through blockade of IL-4R alpha, dupilumab modulates signaling of both the IL-4 and IL-13 pathways, which have been implicated in the pathophysiology of Th2 mediated, or allergic, diseases such as asthma,” said George D. Yancopoulos, M.D., Ph. D., Chief Scientific Officer of Regeneron and President of Regeneron Laboratories. “These data, combined with our previously-reported positive proof-of-concept clinical results of dupilumab in atopic dermatitis, support the idea that blocking the IL-4/IL-13 pathway may be an effective mechanism to treat multiple allergic conditions. We look forward to initiating Phase 2b studies in both asthma and atopic dermatitis shortly.”
These data will be presented by Dr. Sally Wenzel this morning at the American Thoracic Society 2013 International Conference in a presentation entitled, “Efficacy and safety of SAR231893/REGN668 in patients with moderate-to-severe, persistent asthma and elevated eosinophil levels.”
About IL-4R and the IL-4/IL-13 Pathway
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.
About Dupilumab (SAR231893/REGN668)
Dupilumab 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 pioneering VelocImmune(®) technology and is being co-developed with Sanofi. Dupilumab is currently being studied in both atopic dermatitis and asthma.
Asthma is a chronic inflammatory disease of the airways characterized by airway sensitivity to environmental and biologic factors such as dust, chemicals, smoke, allergens, and viral infections leading to an acute and chronic narrowing of the airway and increased mucus production. Patients with asthma can experience wheezing, shortness of breath, cough and chest tightness, and in severe cases, these symptoms can be life-threatening. For most asthma patients, currently available treatments can control the disease. However, an estimated 10% to 20% of asthmatic patients are less than optimally controlled despite existing therapies. Moderate-to-severe asthma can negatively impact the lives of patients and is associated with a high burden to society both in terms of direct costs of medical care and prescription drugs, as well as loss of productivity. Moderate-to-severe asthma is recognized as a heterogeneous disease; the Th2 inflammation pathway is believed to play a role in disease pathogenesis in approximately 50% of these patients. It is estimated that approximately 25 million people in the United States are known to have asthma. The worldwide estimates are between 235-300 million people, with 180,000 deaths annually.
Sanofi, an integrated global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and the new Genzyme. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
About Regeneron Pharmaceuticals, Inc.
Regeneron is a leading science-based biopharmaceutical company based in Tarrytown, New York that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions. Regeneron markets medicines for eye diseases, colorectal cancer, and a rare inflammatory condition and has product candidates in development in other areas of high unmet medical need, including hypercholesterolemia, oncology, rheumatoid arthritis, allergic asthma, and atopic dermatitis. For additional information about the company, please visit www.regeneron.com.
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