Title : Efficacy of varenicline solution nasal spray (VNS) 0.03mg on signs and symptoms of dry eye disease: ONSET 1, ONSET 2, and MYSTIC trials
Abstract:
Purpose: Dry Eye Disease (DED) is a multifactorial, chronic disease characterized by a persistently unstable and/or deficient tear film leading to visual discomfort or impairment, with varying degrees of neurosensory abnormalities, inflammation, and ocular surface epitheliopathy. VNS?is a preservative-free, cholinergic agonist delivered intranasally twice daily to increase basal tear production by stimulating the trigeminal parasympathetic pathway. Its novel mechanism of action allows the tear film to be restored to homeostasis with natural tear production. The Phase 2 (ONSET-1 and MYSTIC) and 3 (ONSET-2) clinical trials evaluated the efficacy and safety of VNS in treating the signs and symptoms of DED.
Methods: The trials were randomized, double-masked, and vehicle controlled (VC) for 1063 subjects. 349 subjects were randomized to receive 0.03mg VNS and 336 to VC for 28 days in ONSET-1 and ONSET-2 and 84 days in MYSTIC. Outcome measures included anesthetized Schirmer’s Test Score (STS) and Eye Dryness Score (EDS, 0-100 scale). Symptoms were not evaluated in MYSTIC.
Results: VNS 0.03mg demonstrated a statistically significant (p<0.001) improvement in mean change in percent of subjects with ≥10 mm increase in STS and mean change in STS from baseline to Day 28 compared to VC in ONSET-1 and ONSET-2. Consistent effect (p<0.05) was seen in MYSTIC at Day 84. VNS 0.03mg showed statistical significance (p<0.05) in mean change from baseline to Day 28 in EDS in the clinic environment in ONSET-1.
Conclusions: The US FDA-approved VNS 0.03mg nasal spray was well tolerated and improved both signs and symptoms of DED in three clinical trials. This novel method of delivery of an effective dry eye therapy is planned to be launched in multiple countries around the world.
