FDA Accepts Reproxalap NDA for Dry Eye Disease

The U.S. Food and Drug Administration (FDA) has accepted for review Aldeyra Therapeutics’ resubmitted New Drug Application (NDA) for reproxalap, an investigational therapy intended to treat the signs and symptoms of dry eye disease (DED). A Prescription Drug User Fee Act (PDUFA) target action date has been set for December 16, 2025.

Resubmission Follows Prior Complete Response Letter

This NDA resubmission follows Aldeyra’s receipt of a second Complete Response Letter (CRL) from the FDA, issued three months prior. The CRL noted methodological concerns in a previously conducted dry eye chamber trial, including baseline imbalances across treatment arms, which may have impacted interpretation of the efficacy results. The FDA stated that an additional symptom trial would be necessary for reconsideration of approval.

In response, Aldeyra resubmitted the NDA with data from a newly completed clinical trial that addressed the agency’s concerns and met the primary efficacy endpoint.

Positive Phase 3 Trial Data Supports Resubmission

In May 2025, Aldeyra announced successful results from a phase 3 randomized, double-masked, vehicle-controlled dry eye chamber trial evaluating reproxalap’s ability to reduce ocular discomfort. The trial demonstrated that reproxalap (n=58) was statistically superior to vehicle (n=58) in reducing ocular discomfort scores between 80 and 100 minutes after chamber entry.

The least squares mean difference in ocular discomfort was 6.5 (95% CI: -10.5, -2.5; P=0.002), confirming the therapy’s significant effect in acute DED flare simulation. No safety concerns were identified in the trial. The most commonly reported adverse event was mild, transient instillation site discomfort, which typically resolved in under one minute.

Aldeyra Comments on the Review Process

Dr. Todd C. Brady, President and CEO of Aldeyra, commented:
“Based on the FDA’s requirement for an additional clinical trial demonstrating the efficacy of reproxalap in treating the symptoms of dry eye disease, and per agreement with the FDA, the NDA resubmission contained a single clinical trial that achieved the primary endpoint of reducing ocular discomfort relative to the vehicle control. We look forward to a productive dialog with the FDA during the NDA review of reproxalap, which, to our knowledge, remains the only dry eye disease investigational therapy to have demonstrated acute activity in reducing ocular discomfort and redness in pivotal trials simulating the disease flares that are likely the most bothersome aspects of dry eye disease.”