Lifitegrast Ophthalmic Solution 5.0% for Treatment of Dry-Eye Disease: Results of a Phase 3 Randomized Masked Controlled Trial
Narrative Responses:
Purpose
Lifitegrast (LIF) is a novel ICAM-1 decoy that targets chronic inflammation in dry eye disease (DED). An earlier Phase 3 trial (OPUS-1) demonstrated that LIF improved certain signs and symptoms of DED vs placebo (PBO). We report results of OPUS-2, a Phase 3, multicenter, randomized, double-masked, PBO-controlled trial (NCT01743729).
Methods
Adult subjects with DED and recent artificial tear use were randomized after 14-day PBO run-in period 1:1 to topical LIF 5.0% or PBO (vehicle) twice daily for 84 days. Co-primary efficacy endpoints (EPs) were inferior corneal staining (ICSS; 0–4 points; 0=no stain) in study eye and eye dryness (EDS; 0–100 points; 0=no symptoms); secondary EPs were total corneal staining (TCS; 0–12 points; 0=no stain) and nasal lissamine staining (NLS; 0–4 points; 0=no stain); ocular discomfort (ODS; 0–4 points, 0=no symptoms) and eye discomfort (EDIS; 0–100 points, 0=no symptoms). All variables were analyzed by mean change from baseline to Day 84. Treatment-emergent adverse events (TEAEs) were assessed.
Results
718 subjects were randomized (358 LIF; 360 PBO). For ICSS, no between-group difference was observed (difference 0.03; 95% CI: -0.10, 0.17; P=0.6186). For EDS, the LIF group had significantly greater mean reduction vs PBO (diff 12.61; 95% CI: 8.51, 16.70; P<0.0001). Outcomes for secondary EPs comparing LIF vs PBO were (signs) TCS: diff 0.14 (95% CI: -0.16, 0.44), NLS: diff -0.02 (95% CI: -0.14, 0.10); (symptoms) ODS: diff 0.34 (95% CI: 0.15, 0.53), EDIS: diff 9.77 (95% CI: 5.27, 14.28). There were no serious ocular TEAEs. TEAEs (≥5% of subjects) were dysgeusia (LIF 16.2%; PBO 0.3%), instillation site irritation (7.8%; 1.4%) and reaction (7.0%; 1.1%), and reduced visual acuity (5.0%; 6.4%).
Conclusion
In this trial, LIF-treated subjects experienced significant improvement in the co-primary symptom EP but not the co-primary sign EP vs PBO-treated subjects. Secondary outcomes in signs and symptoms consistently supported the co-primary EPs. Lifitegrast appeared to be well tolerated in this trial.