FDA Accepts Reproxalap Application for Dry Eye Disease

The US Food and Drug Administration (FDA) has accepted for review the resubmitted New Drug Application (NDA) of reproxalap to treat dry eye disease (DED).1

Announced on July 17 by parent company Aldeyra Therapeutics, Inc., the FDA has also assigned a Prescription Drug User Fee Act (PDUFA) target action date for December 16, 2025.1

“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,” said Todd C. Brady, MD, PhD, president and chief executive officer of Aldeyra.1

A first-in-class small-molecule modulator of RASP, reproxalap has had an uphill battle for approval, receiving multiple Complete Response Letters (CRLs) over the course of 3 years. The first came in November of 2023, citing a failure to demonstrate efficacy in treating ocular symptoms associated with dry eyes. Aldeyra resubmitted reproxalap’s NDA on October 3, 2024, including a draft label reflecting acute activity in reducing DED symptoms in a dry eye chamber trial, chronic activity in reducing symptoms in a field trial, and acute activity in reducing ocular redness in 2 chamber trials.2

The FDA issued another CRL in April 2025, citing potential methodological issues in a prior dry eye chamber trial – namely a baseline difference across treatment arms – which may have influenced the interpretation of the results. Accordingly, the FDA required another symptom trial for resubmission.4

In May 2025, Aldeyra announced the achievement of the primary endpoint in a phase 3 randomized, double-masked, vehicle-controlled dry eye chamber trial. Assessing the activity of reproxalap in reducing ocular discomfort, an FDA accepted symptom of DED, the trial exhibited no significant differences in baseline scores across treatment arms and no safety concerns in treatment. The most common adverse event was mild and transient installation site discomfort often lasting <1 minute.4

“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,” Brady said.1

References

1. Aldeyra Therapeutics, Inc. Aldeyra Therapeutics Announces FDA Acceptance for Review of Reproxalap New Drug Application for the Treatment of Dry Eye Disease. Businesswire. July 17, 2025. Accessed July 17, 2025. https://www.businesswire.com/news/home/20250717410973/en/Aldeyra-Therapeutics-Announces-FDA-Acceptance-for-Review-of-Reproxalap-New-Drug-Application-for-the-Treatment-of-Dry-Eye-Disease

2. Aldeyra Therapeutics Resubmits Reproxalap New Drug Application for the Treatment of Dry Eye Disease. Aldeyra Therapeutics, Inc. June 17, 2025. Accessed July 17, 2025. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-resubmits-reproxalap-new-drug-application-0

3. Iapoce C. Aldeyra Resubmits New Drug Application for Reproxalap for Dry Eye Disease. HCPLive. October 3, 2024. Accessed July 17, 2025. https://www.hcplive.com/view/aldeyra-resubmits-new-drug-application-reproxalap-dry-eye-disease

4. Livingston R. FDA Issues Complete Response Letter to Reproxalap for Dry Eye Disease. HCPLive. April 3, 2025. Accessed July 17, 2025. https://www.hcplive.com/view/fda-issues-complete-response-letter-to-reproxalap-for-dry-eye-disease