Inhaled pan-selectin antagonist Bimosiamose attenuates airway inflammation in COPD

Selectins, a family of cell adhesion molecules, are involved in leukocyte extravasation to sites of inflammation. We investigated the safety and efficacy of the inhaled pan-selectin antagonist Bimosiamose in patients with chronic obstructive pulmonary disease (COPD).77 COPD patients (mean forced expiratory volume in 1 s, 57% pred.) were enrolled in a cross-over, double-blind, randomized, Placebo-controlled, multi-center trial. Bimosiamose (10 mg) or Placebo was inhaled twice daily via the breath actuated nebulizer Akita2 Apixneb™ for 28 days on top of standard bronchodilator therapy. Efficacy was assessed by measurement of inflammatory parameters in induced sputum (differential cell count, interleukin-8, matrix-metalloproteinase-9, myeloperoxidase) and lung function at day 28 of both treatment periods.The total adverse event ratio of Bimosiamose compared to Placebo treatment was balanced. Compared to Placebo, treatment with Bimosiamose led to a decrease of the interleukin-8 concentration (−9.49 ng/mL, 95%CI −18.8 to −2.7 ng/mL, p = 0.008), for the neutrophil count a difference of −0.368 × 106 cells/mL (95%CI −1.256 to 0.407 × 106/mL, p = 0.313) was found. The macrophage count decreased by −0.200 × 106 cells/mL (95%CI −0.365 to −0.044 × 106 cells/mL, p = 0.012). Most lung function parameters showed a small numeric increase.Inhalation of Bimosiamose for 28 days was safe and well tolerated in patients with COPD. It led to an attenuation of airway inflammation (EudraCT 2009-017257-35; NCT ID: NCT01108913).