Lifitegrast Ophthalmic Solution 5.0% for Treatment of Dry-Eye Disease: Results of a Phase 3 Randomized Masked Controlled Trial

Sunday, April 27, 2014: 2:08 PM
Room 150 (Boston Convention and Exhibition Center)
Joseph Tauber, MD, Tauber Eye Center, Kansas City, MO, USA
Charles P. Semba, MD, Shire, Brisbane, CA, USA
Aparna Raychaudhuri, PhD, Shire, Wayne, PA, USA

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.