FDA accepts for review Aldeyra Therapeutics’ resubmitted New Drug Application for reproxalap

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The US Food and Drug Administration (FDA) has accepted for review the resubmitted New Drug Application (NDA) for topical ocular reproxalap for the treatment of signs and symptoms of dry eye disease from Aldeyra Therapeutics.¹

Aldeyra resubmitted its NDA to the FDA in June 2025² after it received 2 complete response letters (CRL) from the FDA in April 2025 and November 2023 for past submissions.

In the CRL at the end of 2023,³ 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.

In the NDA issued in April 2025,⁴ 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.

Todd C. Brady, MD, PhD, president and CEO of Aldeyra, commented on the FDA acceptance for review in a press release from the company.

“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 Brady. “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.”

The trial mentioned by Brady is the recently completed dry eye chamber trial, which achieved the primary end point.⁵ The dry eye chamber trial was statistically superior to the vehicle in terms of ocular discomfort, and although the field trial missed statistical significance for the primary endpoint, the company noted it was consistent with previous field trials. As previously reported,⁵ the FDA accepts chamber trial results per its draft guidance for dry eye drug development, but they are rare for dry eye clinical trials

A Prescription Drug User Fee Act (PDUFA) target action date of December 16, 2025, was assigned by the FDA.

References:

1. Aldeyra Therapeutics Announces FDA Acceptance for Review of Reproxalap New Drug Application for the Treatment of Dry Eye Disease. Published July 17, 2025. Accessed July 17, 2025. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-announces-fda-acceptance-review-0

2. Hutton D. Aldeyra Therapeutics receives complete response letter from FDA for reproxalap NDA. Published November 29, 2023. Accessed July 17, 2025. https://www.ophthalmologytimes.com/view/aldeyra-therapeutics-receives-complete-response-letter-from-fda-for-reproxalap-nda

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

4. Harp MD. FDA issues complete response letter to Aldeyra Therapeutics for resubmitted new drug application of reproxalap. April 3, 2025. Accessed July 17, 2025. https://www.ophthalmologytimes.com/view/fda-issues-complete-response-letter-to-aldeyra-therapeutics-for-resubmitted-new-drug-application-of-reproxalap

5. Maharjan EK. Aldeyra Therapeutics hits primary end point in 1 of 2 phase 3 trials for reproxalap. May 7, 2025. Accessed July 17, 2025. https://www.ophthalmologytimes.com/view/aldeyra-therapeutics-hits-primary-end-point-in-1-of-2-phase-3-trials-for-reproxalap