IL-9 blocker appears safe in asthmatics.

CHICAGO -- An investigational fully humanized monoclonal antibody that blocks interleukin-9 cleared an early safety hurdle in patients with asthma.

In a phase II prospective randomized trial, no serious treatment-related adverse events, dose-limiting toxicities, or deaths were reported after a single intravenous dose of Medi-528 or placebo in 30 patients with mild to moderate atopic asthma.

No significant changes in pulmonary function, as measured by spirometry, were reported up to 8 weeks after dosing, Dr. Louis-Philippe Boulet said at the annual meeting of the American College of Chest Physicians.

Medi-528 is currently under development by MedImmune as a potential therapy for asthma, and has been shown in ascending doses up to 9 mg/kg to be safe in healthy volunteers. The current study was sponsored by MedImmune, and Dr. Boulet disclosed no conflicts of interest.

Interleukin-9 (IL-9) is an attractive therapeutic target because the multifunctional cytokine has been shown in experimental models to increase airway inflammation, airway obstruction, airway hyperresponsiveness, mucin production, mast cell generation, and T-helper lymphocyte type 2 (Th2 lymphocyte) and eosinophil accumulation, explained Dr. Boulet, a respiratory specialist at Laval University Hospital Centre, Quebec. Furthermore, blocking IL-9 has reduced airway inflammation and hyperresponsiveness in animal models of asthma.

In the current trial, patients aged 18-65 years with asthma for at least 1 year were randomized to a single IV dose of placebo or Medi-528 at 9 mg/kg. Their baseline PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second) values were 16 mg/mL or less, and their symptoms were adequately controlled on short-acting [[beta].sub.2]-agonists alone to avoid any interference with anti-inflammatory medications, he said.

All patients were followed for 8 weeks, and 21 have been followed for 18 weeks.

The blinded safety analysis revealed 59 events reported by 20 of the 30 patients (67%). Six treatment-related adverse events were reported by three patients; and seven acute events were reported by five patients, including headache, chills, nausea, pyrexia, erythema, and blurred vision. All adverse events were mild to moderate, and resolved without sequelae, Dr. Boulet said. No clinically significant trends in laboratory values were observed.

One serious adverse event--two episodes consistent with convulsions--was reported by a woman a few months after treatment. The safety code for this patient was un-blinded, revealing that she was placebo treated, Dr. Boulet said. Further evaluation by neurologists suggested she likely had preexisting and undiagnosed asymptomatic multiple sclerosis.

BY PATRICE WENDLING

Chicago Bureau