Phase II data show 12-week efficacy of varenicline nasal spray in dry eye disease

The phase II MYSTIC clinical trial for the small-molecule nicotinic acetylcholine receptor agonist varenicline nasal spray (VNS), conducted in Mexico, aimed to assess its efficacy and safety for the treatment of dry eye disease.

Study design

One hundred twenty-three patients were randomized 1:1:1 to receive single doses of VNS 0.03 mg, VNS 0.06 mg, or placebo vehicle twice daily for 12 weeks (84 days). Anesthetized Schirmer’s tests were performed on Days 7, 14, 28, 56, and 84, and scores were compared to those taken at baseline

Outcomes

Both the 0.03- and 0.06-mg dose concentrations of VNS significantly increased tear production from baseline to Day 84 compared with vehicle, with least squares mean changes in Schirmer’s test scores (STS) of 10.8, 11.0, and 6.0 mm, respectively. A greater proportion of patients given VNS than patients given vehicle saw an STS increase of ≥10 mm. Minor treatment-emergent adverse events were reported in 32 patients, with no reports of severe or serious events.

Limitations

The study only assessed STS as a measure of clinical improvement and did not incorporate patient self-reports. Also, Schirmer’s test was conducted only 5 minutes after spray administration; an analysis of tear production over multiple time points thereafter would provide further information. Furthermore, statistical power was limited due to patient loss to follow-up.

Clinical significance

The rapid onset of tear production upon administration suggests the potential for high patient adherence to a VNS regimen. Because patients report speed of relief as a crucial factor driving satisfaction with treatment, it is encouraging that the drug acts within 5 minutes. The treatment also has the advantage of not requiring ocular administration, as the trigeminal nerve which it targets is accessible via the nasal cavity and is conducive to nasal spray delivery.