Fellow Eye Outcomes In Subjects With Dry Eye Disease Following Oc-01 (Varenicline Solution) Nasal Spray Treatment: Integrated Data From Onset-1 (Phase 2B) And Onset-2 (Phase 3) Studies

Dry Eye (DE) is a chronic, multifactorial disease that is characterized by an unstable/insufficient tear film¹. It commonly affects the ocular surface bilaterally; therefore, outcome measures must be considered for both eyes. In the Phase 2b (Onset-1) and Phase 3 (Onset-2) studies, efficacy of OC-01 (varenicline solution) nasal spray (VNS) compared to vehicle control (VC) was analyzed in the study eye and fellow eye.  OC-01 VNS is a cholinergic agonist that mimics the action of the neurotransmitter acetylcholine. The binding action of this molecule to receptors in the nasal cavity sends signals to the lacrimal functional unit (LFU) which activates an increase in basal tear production via the trigeminal parasympathetic pathway.

Onset-1 and Onset-2 were randomized, multi-centered, vehicle-controlled, and double-masked studies. Subjects in Onset-2 were stratified by pre-treatment (baseline) anesthetized Schirmer’s Test Score (STS) (≤5,>5) and Eye Dryness Score (EDS) (<60, ≥60). Primary endpoint for Onset-1 was mean change from baseline (mΔBL) in STS to Week 4 and for Onset-2 was percent of subjects who achieve ≥10 mm improvement in STS from baseline at Week 4.

 

891 subjects were randomized to receive 0.03 mg, 0.06 mg OC-01 VNS or VC once to each nostril BID to Week 4 (W4). Analysis of covariance (ANCOVA) using a last observation carried forward on the Intent to treat population assessed mean changes from baseline in STS at W4 for study eye (SE) and fellow eye (FE). SE was defined as the eye meeting all inclusion/exclusion criteria at screening. If both eyes qualified, the eye with the greatest increase in STS upon mechanical stimulation, or (if no difference) the eye with the lower basal STS, was selected. All subjects enrolled had a baseline STS (with topical anesthesia) score of ≤ 10mm/5 minutes with cotton swab nasal stimulation and <20mm difference from SE to FE STS. 

 

mΔBL in STS at W4 were greater for OC-01 treated eyes compared to VC. Integrated data for Onset-1 and Onset-2 by treatment groups, 0.03 mg, 0.06 mg, and VC have a mean baseline STS for SE to be 5.1 mm, 5.4 mm, and 4.8 mm and FE to be 7.23 mm, 8.30 mm, 7.44 mm, respectively. SE outcomes (p<0.0001) for 0.03 mg, 0.06 mg and VC were as follows:10.4 mm, 10.5 mm, and 4.9 mm, respectively. FE outcomes were(p<0.0001): 8.7 mm, 8.8 mm, and 2.7 mm, respectively. OC-01 VNS treated subjects showed statistically significant improvement in percentage of subjects achieving STS of ≥10 mm mΔBL to W4. SE outcomes (p<0.0001): 0.03 mg, 0.06 mg, and VC were: 48.1%, 48.4% and 25.9%, respectively. FE outcomes were(p<0.0001): 42.9%, 43.9%, and 19.7%, respectively.

Pharmacologic neuro-activation via OC-01 VNS demonstrates benefit over VC for the treatment of dry eye disease, bilaterally. The data demonstrates benefit with OC-01 (varenicline solution) nasal spray 0.03 mg and 0.06 mg concentration groups compared to VC in STS outcomes from baseline to Week 4 in both study and fellow eyes. OC-01 was well tolerated and safe under conditions of the study.