Efficacy and Safety of Spleen Tyrosine Kinase and VEGFR-2 Dual-Target Kinase Inhibitor (OT202) in Dry Eye: A Randomized, Vehicle-Controlled Phase 2 Trial.

PURPOSE: To evaluate the efficacy and safety of OT202 (Ocumension Therapeutics [Shanghai] Co, Ltd), a first-in-class, dual-target kinase inhibitor of spleen tyrosine kinase and vascular endothelial growth factor receptor 2, for treating moderate to severe dry eye disease (DED).

DESIGN

Multicenter, randomized, double-masked, vehicle-controlled phase 2 trial.

PARTICIPANTS

Adults with moderate to severe DED of at least 6 months' duration.

METHODS

Patients who remained eligible after a 2-week run-in period were randomized 1:1:1 to receive 0.5% OT202, 1% OT202, or OT202 vehicle 3 times daily for 8 weeks.

MAIN OUTCOME MEASURES: The primary end point was the change from baseline to week 8 in the total corneal staining score (TCSS). Secondary end points included changes in ocular surface disease index (OSDI) score, visual analog scale score, symptom assessment in dry eye score, conjunctival hyperemia score, conjunctival staining score, tear film breakup time, Schirmer I test results, and corneal staining score for each region at weeks 4 and 8.

RESULTS

The 1% OT202 group demonstrated a significantly higher reduction in TCSS score from baseline (least-squares mean [LSM], -1.93 ± 0.23) compared with the vehicle group (LSM, -1.11 ± 0.23) at week 8 (treatment difference, -0.82; 95% confidence interval [CI], -1.46 to -0.18; P = 0.0118). Additionally, 1% OT202 demonstrated significantly greater reduction at week 8 in OSDI score (LSM, -16.25 ± 1.77) compared with the vehicle group (treatment difference, -5.35; 95% CI, -10.16 to -0.54; P = 0.0296), central corneal staining (treatment difference, -0.20; 95% CI, -0.38 to -0.02), and nasal corneal staining (-0.38; 95% CI, -0.66 to -0.11). However, the 0.5% OT202 group showed no significant changes in either primary or secondary outcomes. The most common treatment-related adverse events were eye discharge (2.8%) and eye pruritus (2.8%).

CONCLUSIONS

One percent OT202 significantly improved TCSS scores at week 8 versus the vehicle in patients with DED. Additionally, OT202 exhibited favorable safety and tolerability. These results suggest 1% OT202's potential in treating DED and support further evaluation.

FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.