Inhalation of the anti-interleukin-13 (IL-13) mononclonal antibody Fab fragment, CDP7766, via the investigational eFlow® nebulizer system (PARI Pharma GmbH; Gräfelfing, Germany) inhibited allergen-induced lung inflammation and pulmonary responses in a model of asthma in cynomolgus macaques according to the results of a study published in the American Journal of Respiratory and Critical Care Medicine.
The cytokine IL-13 is known to have a role in the pathogenesis of allergic asthma and thus is an important therapeutic target. Greater concentrations of this cytokine are observed in severe asthma and during exacerbations. IL-13 is known to stimulate the airway epithelium, causing hyperplasia, mucus secretion, and the generation of proinflammatory cytokines. Evidence also suggests that IL-13 activates fibroblasts, mast cells, and airway smooth muscles.
Daniel Lightwood, PhD, director of antibody discovery at UCB Pharma in Slough, Berkshire, United Kingdom, and colleagues, investigated the efficacy of CDP7766 in cynomolgus macaques naturally sensitized to Ascaris suum. Nebulized CDP7766 was delivered once daily for 5 days via inhalation.
The eFlow® nebulizer delivered CDP7766 without evidence of degradation, loss of potency, aggregation, or formation of particulates. CDP7766 was well tolerated, with no evidence of local irritation. It significantly reduced bronchoalveolar lavage allergen-induced cytokine and chemokine upregulation (P <.0008 and P <.01, respectively). Furthermore, CDP7766 significantly reduced the increase in pulmonary resistance induced by the inhaled allergen as measured at 15 minutes and 24 hours after the allergen challenge.
The eosinophil number did not increase in the cynomolgus macques with administration of CDP7766; although in humans, systemic administration of an anti-IL-13 monoclonal antibody has been associated with elevated eosinophil counts, pointing to a possible class effect with systemic administration.
The investigators noted that further corroboration in human studies is needed and the longer-term effects of CDP7766 must be established.
Disclosures: This study was funded by UCB Pharma where several authors are employed.
Lightwood D, Tservistas M, Zehentleitner M, et al. Efficacy of an inhaled interleukin-13 antibody fragment in a model of chronic asthma [published online June 8, 2018]. Am J Respir Crit Care Med. doi:10.1164/rccm.201712-2382OC