A SINGLE DOSE OF MEDI-528, A MONOCLONAL ANTIBODY AGAINST INTERLEUKIN-9, IS WELL TOLERATED IN MILD AND MODERATE ASTHMATICS IN THE PHASE II TRIAL MI-CP-138

Abstract

PURPOSE: Interleukin-9 (IL-9) increases airway inflammation, obstruction and hyperresponsiveness, mucin production, mast cell generation, and Th2 lymphocyte and eosinophil accumulation in experimental systems. Conversely, blocking IL-9 reduces airway inflammation and hyperresponsiveness in animal models of asthma. Thus, blocking IL-9 may provide benefit in asthma. MEDI-528, a humanized, anti-interleukin-9 (IL-9) monoclonal antibody, is currently in development by MedImmune, Inc. as a potential therapy for asthma. Single ascending doses of MEDI-528, up to 9 mg/kg, have been shown to be safe in healthy volunteers. The current report summarizes the first clinical experience in asthmatics. METHODS: MI-CP138 is an on-going Phase 2a, randomized, double blind, placebo-controlled study of the effect of single intravenous doses of MEDI-528, 9 mg/kg, in patients with mild and moderate atopic asthma and dual asthmatic response. Patients symptoms are adequately controlled with the use of short-acting beta2 agonists alone. The 9 mg/kg dose provides expected blockade of IL-9 for weeks, given the long T1/2 of 26 days. This report summarizes the blinded safety information from the first 10 patients in the study, through completion of Study Day 28. RESULTS: No serious adverse events (SAEs) have been reported. There have been no reports of deaths, interruptions of study drug administration, discontinuations due to adverse events (AEs), or anaphylaxis. Five (50%) of the 10 patients have reported a total of 5 treatment-emergent AEs: chills, erythema, headache, nasopharyngitis and nausea, each reported by one patient. All AEs were mild to moderate, and all resolved without sequelae. One AE, erythema of moderate severity, was considered by the investigator as related to study drug (MEDI-528 or placebo). No clinically significant trends in laboratory values were observed, and all abnormalities were mild or moderate in severity. Pulmonary function, as measured by spirometry (FEV1, FVC) did not experience any significant change 1 and 4 weeks after dosing. CONCLUSION: A single dose of MEDI-528 appears well tolerated in patients with mild and moderate atopic asthma. CLINICAL IMPLICATIONS: MEDI-528 merits futher evaluation as a potential therapy for asthma. DISCLOSURE: Louis-Philippe Boulet, Employee Francisco Leon is an employee of MedImmune, Inc.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. MEDI-528 in an investigational product.