Nasal spray eases signs, symptoms of dry eye disease

The varenicline-containing nasal spray OC-01 appears beneficial in the treatment of dry eye disease, producing improvements in natural tear film production and patient-reported symptoms with a tolerable safety profile, as shown in the phase III trial ONSET-2.

Significantly more patients achieved a clinically meaningful improvement in the main sign of dry eye disease (≥10-mm increase in Schirmer’s Test Score [STS]) after 4 weeks of treatment with OC-01 compared with vehicle (OC-01 0.6 mg/ml, 47.3 percent; OC-01 1.2 mg/ml, 49.2 percent; vehicle, 27.8 percent; p<0.0001 for both comparisons). [Ophthalmology 2021;doi:10.1016/j.ophtha.2021.11.004]

Furthermore, this improvement in the production of tear film was observed regardless of the baseline severity of tear production or eye dryness symptoms (EDS).

In terms of safety, OC-01 was well tolerated, with the most common adverse events being mild transient sneezing, cough, throat irritation, and instillation site irritation.

“This is the first phase III study to investigate whether OC-01 nasal spray containing the highly selective nicotinic acetylcholine receptor (nAChR) agonist, varenicline, a pharmacologic neuro-activator, can increase tear film production in patients with dry eye disease,” according to the investigators.

They stressed that tear film production is an important consideration, citing reports indicating that a decrease in this production, in addition to a subsequent increase in inflammatory markers and corneal fluorescein staining (CFS), is an initial contributing factor to the development of dry eye disease and increased tear film hyperosmolarity. [Mol Vis 2009;15:250-258; Cornea 2007;26:579-584; Ocul Surf 2017;15:276-283]

“Our results suggest that the novel OC-01 nasal spray treatment can activate the trigeminal parasympathetic pathway to promote tear film production and improve symptoms and may have potential for benefit across the spectrum of dry eye disease severity,” the investigators said.

ONSET-2 included 758 adults dry eye disease (average age 59 years, 76 percent women), who were randomized to twice-daily treatment with 50-μl intranasal spray in each nostril of OC-01 0.6 mg/ml (n=260), OC-01 1.2 mg/ml (n=246), or vehicle (n=252) for 4 weeks. All patients used artificial tear at baseline and had an Ocular Surface Disease Index score of ≥23 or more and STS of ≤10 mm.

Despite the presence of limitations, ONSET-2 presented findings consistent with those reported from the phase 2b ONSET-1 study. Moreover, relative to previous studies evaluating other therapies for dry eye disease, ONSET-2 indicated that the benefit of OC-01 was comparable and might even occur sooner. [Holland E, American Society for Cataract and Refractive Surgery Annual Meeting 2019; Cochrane Database Syst Rev 2019;9:CD01005; Curr Med Res Opin 2005;21:1057-1063]

“The route of administration of OC-01 nasal spray offers many advantages over traditional topical therapies,” according to the investigators.

First is the avoidance of the ocular surface, which may reduce painful instillation of drops in irritated eyes. Administration via a nasal spray also provides a potentially easier delivery method for some patients, they said. Finally, the stimulation of tear film production via a pathway that is independent of the nerves of the ocular surface can benefit some patients with chronic diseases who may have damaged ocular surface nerves.