FDA extends Aldeyra's reproxalap PDUFA after requesting additional clinical study report

The US Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) target action date for Aldeyra’s New Drug Application (NDA) for reproxalap for the treatment of dry eye disease (DED). The new target action date is March 16, 2026—pushed back from December 16, 2025.¹

Aldeyra met with the FDA on December 12, 2025, in which the FDA requested the company submit the Clinical Study Report (CSR) from the reproxalap DED field trial to the NDA, following the announcement of topline results on May 5, 2025. The field trial did not meet the primary endpoint of improvement in dry eye symptoms relative to the vehicle control. However, according to the company, the trial was supportive of the activity of reproxalap relative to vehicle. The company also noted that the field trial was discussed with the FDA prior to the resubmitted NDA in June 2025.

According to Aldeyra, the FDA made no other requests and did not identify any other specific issues with the NDA review during their meeting on December 12, 2025. Aldeyra noted that the CSR was submitted to the NDA the same day as the meeting with the FDA and was considered a major amendment to the NDA by the FDA. Safety data from the field trial was submitted to the NDA on August 21, 2025.

Aldeyra stated the FDA notified the company that if no major deficiencies are identified during the extended review, it plans to communicate proposed labeling requests and, if necessary, any anticipated postmarketing requirements by February 16, 2026.

Reproxalap's journey to possible approval

Aldeyra received its first Complete Response Letter (CRL) from the FDA for reproxalap in November 2023.²

In the CRL at the end of 2023, the FDA identified no safety or manufacturing issues with reproxalap but noted the NDA did not demonstrate “efficacy in treating ocular symptoms associated with dry eyes” and that “at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye” should be conducted.³

Following the first CRL,² Aldeyra submitted a second NDA to the FDA in October 2024.⁴ The new NDA featured previously disclosed positive results from a completed DED symptom trial that was requested by the FDA following a review of the previous NDA. The application also included a draft label reflecting:

• Acute activity in reducing dry eye symptoms in a dry eye chamber trial
• Chronic activity in reducing dry eye symptoms in a field trial
• Acute activity in reducing ocular redness in 2 dry eye chamber trials

The FDA issued a second CRL to Aldeyra in April 2025.⁵ In this CRL, again the FDA found no manufacturing or safety issues with reproxalap but noted that the NDA “failed to demonstrate efficacy in adequate and well-controlled studies in treating ocular symptoms associated with dry eyes” and that “at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye” should be conducted, mirroring the prior CRL.

Aldeyra then resubmitted its third NDA for reproxalap in June 2025, which was accepted for review by the FDA in July of the same year.⁶ A PDUFA date of December 16, 2025, was set, which has since been delayed.

References:

1. Aldeyra Therapeutics Announces PDUFA Extension of the New Drug Application of Reproxalap for the Treatment of Dry Eye Disease. Published December 15, 2025. Accessed December 16, 2025. https://www.businesswire.com/news/home/20251215293677/en/Aldeyra-Therapeutics-Announces-PDUFA-Extension-of-the-New-Drug-Application-of-Reproxalap-for-the-Treatment-of-Dry-Eye-Disease

2. Hutton D. Aldeyra Therapeutics receives complete response letter from FDA for reproxalap NDA. Published November 29, 2023. Accessed December 16, 2025. https://www.ophthalmologytimes.com/view/aldeyra-therapeutics-receives-complete-response-letter-from-fda-for-reproxalap-nda

3. Harp MD. FDA accepts for review Aldeyra Therapeutics’ resubmitted New Drug Application for reproxalap. Published July 17, 2025. Accessed December 16, 2025. https://www.ophthalmologytimes.com/view/fda-accepts-for-review-aldeyra-therapeutics-resubmitted-new-drug-application-for-reproxalap

4. Harp MD. Aldeyra Therapeutics resubmits New Drug Application for reproxalap for the treatment of dry eye disease. Published October 3, 2024. Accessed December 16, 2025. https://www.ophthalmologytimes.com/view/aldeyra-therapeutics-resubmits-new-drug-application-for-reproxalap-for-the-treatment-of-dry-eye-disease

5. Harp MD. FDA issues complete response letter to Aldeyra Therapeutics for resubmitted new drug application of reproxalap. April 3, 2025. Accessed December 16, 2025. https://www.ophthalmologytimes.com/view/fda-issues-complete-response-letter-to-aldeyra-therapeutics-for-resubmitted-new-drug-application-of-reproxalap

6. Harp MD. Aldeyra submits third new drug application for reproxalap for the treatment of dry eye disease. Published June 17, 2025. Accessed December 16, 2025. https://www.ophthalmologytimes.com/view/aldeyra-submits-third-reproxalap-new-drug-application-for-the-treatment-of-dry-eye-disease