Efficacy and safety of inhaled ENaC inhibitor BI 1265162 in patients with cystic fibrosis: BALANCE-CF™ 1 - a randomised, Phase II study.

Abstract

BACKGROUND\nInhibition of the epithelial sodium channel (ENaC) in cystic fibrosis (CF) airways provides a mutation-agnostic approach that could improve mucociliary clearance in all CF patients. BI 1265162 is an ENaC inhibitor with demonstrated preclinical efficacy and safety already demonstrated in humans.\n\n\nOBJECTIVE\nWe present results from BALANCE-CF™ 1, a Phase II, placebo-controlled, randomised, double-blind study of four dose levels of BI 1265162 versus placebo for 4\u2005weeks on top of standard of care in adults and adolescents with CF.\n\n\nRESULTS\nInitially, 28 randomised subjects (n=14 each BI 1265162 200\u2005µg BID, placebo BID) were assessed at an interim futility analysis. Compared with placebo, numerical changes of -0.8% (95%CI -6.6, 4.9) in ppFEV1 and +2.1 units (95%CI -2.4, 6.5) in LCI were observed in the active group, meeting a predefined stopping rule; accordingly, the study was terminated. Recruitment had continued during the interim analysis and pending results; 24 patients were added across three dose levels and placebo. The final results including these patients (+1.5% ppFEV1, 200\u2005µg BID dose versus placebo) were not supportive of relevant clinical effect. LCI change was also not supportive, although interpretation was limited due to insufficient traces meeting quality criteria. A 9.4-point improvement in CFQ-R Respiratory Domain was observed in the 200\u2005µg BID dose group versus placebo. BI 1265162 up to 200\u2005µg BID was safe and well-tolerated. Pharmacokinetics were similar to those in healthy volunteers.\n\n\nCONCLUSION\nBI 1265162 was safe, but did not demonstrate a potential for clinical benefit. Development has been terminated.