VX-371 (formerly P-1037) is an inhaled epithelial sodium channel (ENaC) inhibitor being developed by Vertex Pharmaceuticals (in collaboration with Parion Sciences) that blocks the sodium channel in airway cells. By blocking this channel, VX-371 may prolong the duration and maintenance of fluid in the airways after hypertonic saline use. Additional fluid in the lungs aids in making mucus thinner and easier to clear.1

Studies Involving VX-371

An exploratory 14-day Phase 2 study for VX-371 evaluated 136 CF patients, ages 12 and older and regardless of CFTR mutation, who were treated with VX-371 or placebo. Enrolled patients were not taking any kind of CFTR modulator therapy before or during the study. Results confirmed the drug’s safety compared to placebo, a primary study outcome, demonstrating that VX-371 is generally well-tolerated.No significant changes were seen in treated patients in a secondary trial goal, the effect on mean absolute forced expiratory volume in one second (FEV1).

Currently, there are two VX-371 studies recruiting participants. One is a placebo-controlled Phase 2a study  evaluating VX-371 in combination with Orkambi, with or without the addition of hypertonic saline (NCT02709109), in patients with two copies of the F508del-CFTR mutation. Its primary objectives are safety and mean absolute change in FEV1 at day 28, compared to placebo.

An in vitro study showed that VX-371 had a change in cilia beat frequency when used in combination with Orkambi in human bronchial epithelial cells with two copies of F508del mutation, but did not show a significant change when VX-371 was used alone.2

The other study, also Phase 2, is evaluating the safety and efficacy of treatment with VX-371 and its effect on the quality of life (QoL) in people with primary ciliary dyskinesia (PCD) (NCT02871778), a condition that shares similar characteristics with CF. Both CF and PCD have similar effects on the lungs, with mucus accumulation that cause infections and congestion. But the two diseases have different roots: PCD is due to a malfunction of the cilia, the “brooms” that sweep mucus out of the respiratory tract, while people with CF produce abnormal sticky mucus.3

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  1. https://www.cff.org/Trials/Pipeline/details/10139/VX-371-formerly-P-1037
  2. http://investors.vrtx.com/releasedetail.cfm?ReleaseID=967156
  3. http://healthier.stanfordchildrens.org/en/rare-disease-day-pcd-looks-like-cystic-fibrosis-isnt/