NCX 1020 is a nitric oxide (NO)-donating derivative of budesonide, a corticosteroid which is administered by inhalation for the long-term treatment of asthma, where it has been shown to reduce airway inflammation and the risk of asthma attack.
The trial results suggest NCX 1020 may have enhanced activity at counteracting bronchoconstriction (constriction of the muscles surrounding the airways) and the potential for reduced systemic side effects compared to existing inhaled corticosteroids.
The primary objective of the trial was to compare the ability of NCX 1020, budesonide and placebo to relax the bronchial smooth muscle of the airways following methacholine-induced airway narrowing.
NCX 1020 showed a trend at the four-hour time point in protecting against bronchoconstriction. This finding is significant as budesonide does not offer protection against bronchoconstriction on this timescale.
Pharmacokinetic data from the trial demonstrates that administration of NCX 1020 leads to lower levels of budesonide in the systemic circulation than administration of the equimolar dose of marketed budesonide, suggesting NCX 1020 may have the potential for reduced systemic side-effects compared to the currently marketed inhaled corticosteroids.
Inhaled corticosteroids have been linked to a number of systemic side-effects including growth retardation, acne and other skin problems, osteoporosis and glaucoma.
Peak levels of budesonide in the circulation were also delayed with NCX 1020, as compared to marketed budesonide, which may suggest that NO-budesonide is held in the lungs for longer. This possible prolongation in the lung residence time, combined with the increased protection against bronchoconstriction, could have advantages in terms of level and duration of activity.