Long-Term Safety of Reproxalap in Dry Eye Disease

Key Takeaways

• No treatment-related serious TEAEs were reported, and no safety concerns were identified in the treated population.
• Transient, mild instillation site irritation was the most common reproxalap-associated TEAE, and other ocular TEAEs were similar between groups.
• A post hoc BCVA analysis in the 12-month safety population showed greater improvement with reproxalap than with vehicle.

Long-term safety was the focus of a phase 3 reproxalap trial in dry eye disease, a multicenter, double-masked, randomized, vehicle-controlled safety study. The trial enrolled and treated 757 patients, including 504 assigned to reproxalap 0.25% ophthalmic solution and 253 assigned to vehicle. Across treatment periods extending to 6 weeks or 12 months, no treatment-related serious TEAEs were reported. A separate post hoc visual acuity finding is described later.

Eligible patients with dry eye disease were randomized 2:1 to bilateral treatment with reproxalap 0.25% ophthalmic solution or vehicle in a parallel-group design. Treatment was given four times daily for the first 4 weeks, then twice daily for either 2 weeks or 11 months, corresponding to total treatment periods of 6 weeks or 12 months. The primary endpoint was the occurrence of treatment-related serious ocular TEAEs. Prespecified safety assessments included TEAEs, slit-lamp biomicroscopy, dilated fundoscopy, BCVA, intraocular pressure, corneal endothelial cell density, and laboratory testing across short-term and longer-term follow-up.

No treatment-related serious TEAEs were observed during the study, consistent with the primary safety endpoint. The most common reproxalap-associated event was transient, mild instillation site irritation, which most often lasted less than 1 minute. Other ocular TEAEs were reported at similar rates in the reproxalap and vehicle groups. In the 12-month arms, 111 patients receiving reproxalap and 72 receiving vehicle completed the trial. No safety concerns were identified in the treated population.

A post hoc analysis of change from baseline in BCVA within the 12-month safety population showed greater improvement with reproxalap than with vehicle (p=0.0185). That visual acuity result was outside the trial's primary objective, which was safety rather than efficacy. The authors concluded that the findings support the safety of long-term topical reproxalap therapy in dry eye disease.