ENaC blocker enhances mucus clearance in cystic fibrosis models

Child with cystic fibrosis on ventilator

A preclinical study in cystic fibrosis sheep models has demonstrated that low doses of the ENaC blocker ETD001 can enhance airway mucus clearance with a long duration of action.

The study indicates that ETD001, at a dose level that was well tolerated in healthy volunteers, provides an opportunity to test whether a long-acting ENaC blocker can deliver benefit to people with cystic fibrosis (pwCF).

Enterprise Therapeutics is scheduled to commence a Phase II clinical study in pwCF in summer 2024, to understand whether 28 days of treatment will improve lung function.

Blocking ENaC in the airways offers a novel approach to improve mucus clearance in pwCF, including in the more than 10% of individuals who are either intolerant of or genetically unsuited to CFTR modulators.

Recently, several other ENaC blocking drugs (VX-371, AZD5634, BI 1265162, QBW276) failed to show any benefit in clinical trials. This study provides a potential explanation for these failures as data from the sheep model indicate that each may have been dosed in clinical trials at a dose too low to observe an extended duration of action on mucus clearance.

Dr Henry Danahay, Head of Biology, Enterprise Therapeutics, and lead author of the paper, said: “This data provides strong evidence that ETD001 has a superior profile compared to other inhaled ENaC blockers. Along with the results from the Phase I trials where ETD001 was well-tolerated, this study supports our high level of confidence going into the Phase II clinical trial.”

Diana Spencer, Senior Digital Content Editor, DDW

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