Varenicline Solution Nasal Spray: A Review in Dry Eye Disease

Abstract

Increasing endogenous tear film production via pharmacological neuroactivation of the nasolacrimal reflex [NLR; also known as the trigeminal parasympathetic pathway (TPP)] is a novel therapeutic approach to treating dry eye disease (DED). An intranasal formulation of the water-soluble, small-molecule, nicotinic acetylcholine receptor (nAChR) agonist varenicline (Tyrvaya™) has been approved in the USA for the treatment of DED. Twice-daily administration of varenicline solution nasal spray resulted in rapid, statistically significant and clinically meaningful improvements in the signs and symptoms of DED over a period of 4 weeks in two pivotal studies (ONSET-1 and -2). The efficacy of varenicline solution was maintained over a longer-term period of 12 weeks in a third study (MYSTIC). Consistent with the nasal route of delivery, the most common adverse events reported by varenicline solution recipients were non-ocular in nature (mild and transient sneezing and cough). Thus, varenicline solution nasal spray is a rapidly-acting, effective and generally well tolerated treatment for DED that offers several potentially useful advantages over existing topical ocular therapies in terms of increasing endogenous tear secretion and reducing ophthalmic treatment burden.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40265-022-01782-4.

Plain Language Summary

Dry eye disease (DED) is a common, often chronic, condition characterized by symptoms, such as irritation and blurred vision, that can negatively impact on quality of life. DED occurs due to the production of insufficient or unstable tear films and is typically treated with topically applied artificial tears and medications that reduce accompanying inflammation of the ocular surface. Using an intranasal formulation of the nicotinic acetylcholine receptor (nAChR) agonist varenicline (Tyrvaya™) to enhance natural tear production represents a novel approach to DED treatment. Varenicline solution nasal spray led to fast and sustained improvements in the signs and symptoms of DED in clinical trials of up to 12 weeks’ duration. Varenicline solution was also generally well tolerated, with the most common adverse events being mild and transient sneezing and cough. Varenicline solution nasal spray is a new type of treatment for DED that may increase natural tear production, have better ocular tolerability and, for some patients, be easier and/or more convenient to use compared with traditional topical therapies.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40265-022-01782-4.