Abstract
Purpose :
Among patients with dry eye disease (DED), those with systemic autoimmune disease (AID) experience signs and symptoms often more serious with worse treatment effect and prognoses. This analysis evaluated the outcome of DED subjects with documented AID treated with OC-01 (varenicline solution) nasal spray (OC-01 VNS), a cholinergic agonist, compared to vehicle control (VC). OC-01 VNS has been shown to activate the trigeminal parasympathetic pathway to produce basal tear film by stimulating the lacrimal functional unit.
Methods :
In ONSET-1, 182 patients were randomized 1:1:1:1 to receive 0.006 mg, 0.03 mg, or 0.06 mg OC-01 VNS or VC. In ONSET-2, 758 patients were randomized 1:1:1 to receive 0.03 mg or 0.06 mg OC-01 VNS or VC. Subjects administered OC-01 VNS or VC once to each nostril twice daily for 4 weeks. For this sub-population of interest, a total of 31 AID subjects were analyzed based on OC-01 VNS treated (0.03 mg or 0.06 mg, n=20) and VC (n=11) groups. Respectively, OC-01 VNS treated and VC mean baseline (BL) values were Schirmer’s Test Score (STS, mm): 5.6 and 4.2; Eye Dryness Score (EDS, 0-100): 59.2 and 52.7. Outcome measures from BL to Week 4 included STS and mean change in EDS. Differences in OC-01 VNS treated and VC subjects were compared using t-test and chi square tests.
Results :
OC-01 VNS treated subjects showed directional benefit in STS and EDS outcomes compared to VC. For OC-01 VNS treated and VC groups from BL to Week 4, respectively, percentage of eyes demonstrating improvement in STS ≥10 mm: 61.1% and 0.0% (95% CI, 46.0-76.2%); mean change in STS: 13.6mm and 1.8mm (6.5-17.1); and mean change in EDS: -19.6 and -10.3 (-26.8-8.2). OC-01 VNS was well tolerated in the trials. Most common adverse reaction in OC-01 VNS treated groups was sneeze (82-84%); the majority (98%) reported it as mild. Other adverse reactions >5% included cough, throat, and instillation site (nose) irritation.
Conclusions :
In a sub-population with potential to have worse DED, OC-01 VNS treated AID subjects demonstrated directional signaled benefits in DED signs and symptoms at Week 4 compared to VC despite a limited sample size. OC-01 VNS was shown to have a favorable safety and tolerability profile in the trials. Future prospective studies with larger AID subject sample sizes are recommended.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.