BI 1265162

BI 1265162 is a potent, inhaled small molecule inhibitor of the epithelial sodium channel (ENaC), developed for the treatment of cystic fibrosis. By inhibiting ENaC in airway epithelia, it aims to improve mucociliary clearance—a mutation-agnostic approach that could benefit all patients with cystic fibrosis regardless of their specific genetic mutation. Preclinical studies demonstrated that BI 1265162 effectively inhibits sodium ion absorption and reduces water resorption in human and animal models, leading to improved mucociliary clearance without significant effects on renal function or plasma electrolytes. It showed a much higher potency than amiloride, a prototypical ENaC inhibitor[6][7][8]. Clinical trials confirmed its safety profile but failed to demonstrate clinically meaningful efficacy in phase II studies; as a result, development was terminated[1][2][3].