FDA Extends PDUFA Date for Reproxalap in Dry Eye Disease to March 2026

The US Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) target action date for reproxalap in dry eye disease (DED) to March 16, 2026.1

Announced on December 15, 2025, by parent company Aldeyra, this announcement follows a December 12th meeting during which the FDA made no other requests of the company and did not identify any specific issues with the New Drug Application (NDA). The FDA also notified Aldeyra that, if no deficiencies are found during the extended review period, the organization will communicate proposed labeling requests and any anticipated postmarketing requirements by February 16, 2026.1

Reproxalap is a first-in-class small molecule modulator of reactive aldehyde species (RASP), which are elevated in ocular and systemic inflammatory diseases. The drug has hit a series of roadblocks during its path to approval, receiving multiple Complete Response Letters (CRLs) over the course of 3 years. The first came in November 2023, wherein the FDA cited a failure to demonstrate efficacy in treating ocular symptoms associated with dry eyes. In October 2024, Aldeyra resubmitted the NDA with a draft label reflecting acute activity in reducing DED symptoms based on 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

On April 3, 2025, Aldeyra received its second CRL, which highlighted a potential methodological issue in a previous dry eye chamber trial. Citing baseline variance across treatment arms, the FDA suggested that these could have affected the interpretation of the results and requested an additional symptom trial.3

In May 2025, Aldeyra announced the completion of a phase 3 randomized, double-masked, vehicle-controlled dry eye chamber trial, the primary endpoint of which assessed reproxalap’s efficacy in reducing ocular discomfort. This endpoint was achieved, as the 58 patients receiving reproxalap showed significantly lower ocular discomfort symptom scores than the 58 patients receiving vehicle from 80 to 100 minutes after chamber entry (least squares mean difference, -6.5; 95% CI, -10.5 to -2.5; P = .002).4

With these data, Aldeyra sent in the third and latest NDA on June 17, 2025. The FDA accepted it as a “complete class 2 response”, initially setting a PDUFA target action date of December 16, 2025. On December 12, the FDA met with Aldeyra to request submission to the NDA of the Clinical Study Report (CSR) for the DED field trial. This trial did not achieve its primary endpoint of improvement in dry eye symptoms relative to the vehicle control. The FDA considered this a major amendment to the NDA, warranting the PDUFA extension.1

References

1. 1: Nichols L. Aldeyra Therapeutics Announces PDUFA Extension of the New Drug Application of Reproxalap for the Treatment of Dry Eye Disease. Aldeyra Therapeutics. December 15, 2025. Accessed December 16, 2025. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-announces-pdufa-extension-new-drug

2. 2: Livingston R. FDA Accepts Reproxalap Application for Dry Eye Disease. HCPLive. July 17, 2025. Accessed December 16, 2025. https://www.hcplive.com/view/fda-accepts-reproxalap-application-for-dry-eye-disease

3. 3: Nichols L. Aldeyra Therapeutics Resubmits Reproxalap New Drug Application for the Treatment of Dry Eye Disease. Aldeyra Therapeutics. June 17, 2025. Accessed December 16, 2025. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-resubmits-reproxalap-new-drug-application-0

4. Nichols L. Aldeyra Therapeutics Achieves Primary Endpoint in Phase 3 Dry Eye Disease Chamber Trial of Reproxalap and Plans NDA Resubmission. May 5, 2025. Accessed December 16, 2025. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-achieves-primary-endpoint-phase-3-dry-eye-0