Inflammation; pulmonary

Mouse studies suggest an inhaled prodrug of a PI3K inhibitor could help treat asthma and pulmonary fibrosis. In mouse models of acute allergic asthma and chronic asthma, inhalation of a methylbenzoate-based prodrug of a PI3K inhibitor decreased numbers of inflammatory cells in bronchoalveolar lavage and levels of IL-5 and IL-13 - two markers of airway obstruction, hyperresponsiveness and remodeling - in the lung compared with vehicle, with potency comparable to the generic glucocorticoid dexamethasone. Also in the chronic asthma model, inhalation of the prodrug decreased airway, vascular and parenchymal inflammation, and peribronchial fibrotic airway remodeling. In a mouse model of glucocorticoid-resistant neutrophilic asthma, inhalation of the prodrug alone or in combination with intraperitoneal dexamethasone decreased markers of lung damage and numbers of inflammatory cells in bronchoalveolar lavage and increased lung compliance compared with dexamethasone alone. In a mouse model of bleomycin-induced pulmonary fibrosis, inhalation of the prodrug decreased markers of lung damage and fibrosis and increased lung volume and elasticity, expiratory air flow and survival compared with vehicle. Next steps could include optimizing the prodrug formulation for use in patients.

Bayer AG markets the PI3K inhibitor Aliqopa copanlisib for non-Hodgkin lymphoma (NHL) and has the product in Phase II testing for B cell lymphoma and solid tumors and Phase I testing for hepatic insufficiency...