Enhancing Cystic Fibrosis Therapy: The Promise of Inhaled ENaC Blocker NVP-QBE170 in Reducing Hyperkalemia Risk

The study focuses on the development of a new epithelial sodium channel (ENaC) inhibitor, NVP-QBE170, intended for inhalation and designed to mitigate the side effects associated with traditional ENaC blockers such as hyperkalemia. This compound is being explored as a treatment for cystic fibrosis (CF) patients to improve mucociliary clearance (MCC) and lung hydration. The research involved comparing the in vitro potency and duration of NVP-QBE170 with amiloride and another ENaC inhibitor, P552-02, using primary human bronchial epithelial cells. In vivo testing was conducted in guinea pigs, rats, and sheep to evaluate the efficacy and safety of the compound.

Key findings from the study indicate that NVP-QBE170 demonstrated potent inhibition of ENaC function in vitro with a longer-lasting effect compared to other molecules. In vivo, the compound effectively reduced ENaC activity in guinea pig airways, showing a more potent and enduring effect than amiloride without causing hyperkalemia. Additionally, when administered to sheep as a dry powder inhalation, NVP-QBE170 significantly increased MCC, outperforming hypertonic saline in terms of effectiveness and duration.

The conclusions drawn from the study suggest that NVP-QBE170 shows promise as an inhaled ENaC blocker with the potential to be effective in treating airway issues in CF patients while reducing the risk of hyperkalemia compared to existing treatments.