Aldeyra Resubmits Reproxalap NDA for the Treatment of Dry Eye Disease

Aldeyra Therapeutics announced the resubmission of a new drug application (NDA) to the FDA for topical ocular reproxalap for the treatment of signs and symptoms of dry eye disease.

Per FDA agreement, the only new clinical data included in the resubmitted NDA were from the recently completed dry eye chamber trial, which achieved the primary endpoint.

“Consistent with a number of clinical trials that suggest the potential of reproxalap to rapidly improve the symptoms of dry eye disease, we believe the clinical trial results included in the resubmission announced today are robust,” Todd C. Brady, MD, PhD, President and Chief Executive Officer of Aldeyra, said in a company news release. “Based on the lack of notable baseline differences across treatment arms and the highly statistically significant achievement of the prespecified primary endpoint in favor of reproxalap over vehicle, in conjunction with recent FDA discussions, we believe that previous concerns raised by the FDA have been addressed.”

In April 2025, Aldeyra received its second complete response letter (CRL) from the FDA stating that potential methodological issues in a previously completed dry eye chamber trial, including a baseline difference across treatment arms, may have affected the interpretation of the results. The CRL stated that an additional symptom trial would be required for resubmission.

In May 2025, Aldeyra announced the achievement of the primary endpoint (P=0.002) in a phase 3 randomized, double‑masked, vehicle‑controlled dry eye chamber trial that assessed the activity of reproxalap in reducing ocular discomfort. For the prespecified primary endpoint of ocular discomfort, reproxalap (n=58) was statistically significantly superior to vehicle (n=58) on ocular discomfort symptom score (0‑100) from 80 to 100 minutes after chamber entry (LS mean difference [95% confidence interval] ‑6.5 [‑10.5, ‑2.5], P=0.002). No safety concerns were identified. Consistent with prior clinical trials, the most common adverse event was mild and transient instillation site discomfort, which most commonly lasted less than one minute.

The Prescription Drug User Fee Act (PDUFA) target guidelines for NDA resubmissions include acknowledgment of acceptance for review within 30 days of submission, and completion of submission review within 6 months.