FDA issues Complete Response Letter to Aldeyra Therapeutics for resubmitted New Drug Application of reproxalap
The company stated that the FDA noted 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.
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The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Aldeyra Therapeutics for its resubmission of the New Drug Application (NDA) of reproxalap for the treatment of dry eye disease.1
Aldeyra previously conducted 2 trials for ocular redness in a dry eye chamber, and two dry eye disease symptom field (environmental exposure) trials, which were submitted as part of an initial NDA in November 2022.
At the end of 2023, Aldeyra received a CRL for its initial NDA for reproxalap.2 While no safety or manufacturing issues with reproxalap were identified, the FDA stated in the letter that 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.
The FDA accepted the most recent NDA from Aldeyra in November of 2024.3 The new NDA featured previously disclosed positive results from a recently completed dry eye disease symptom trial that was requested by the FDA following a review of the previous NDA. The application also includes 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, and acute activity in reducing ocular redness in 2 dry eye chamber trials.
Again, the FDA found no manufacturing or safety issues with reproxalap. However, the FDA stated in the 2025 CRL that the second NDA submission “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 their previous CRL.
Furthermore, Aldeyra stated the letter identified “concerns with the data from the trial submitted to the NDA that may have affected interpretation of the results,” which the FDA stated may be related to methodological issues, including a difference in baseline scores across treatment arms.
According to the company, a Type A meeting is expected to be held within approximately 30 days to discuss the CRL for the resubmitted NDA and the ongoing clinical trials of reproxalap in dry eye disease.
Todd C. Brady, MD, PhD, president and CEO of Aldeyra Therapeutics commented on the status of the NDA in a press release from the company.
“Pending positive results from the ongoing clinical trials and discussions with the FDA, we look forward to a potential NDA resubmission mid-year 2025,” stated Brady. “Reproxalap remains the only late-stage topical ocular therapy suitable for chronic administration to have potentially demonstrated acute reduction in ocular redness, as well as reduction in ocular discomfort, highlighting rapid and broad activity for both the signs and symptoms of dry eye disease.”
Aldeyra expects to announce top-line results from the ongoing dry eye disease field trial and the ongoing chamber clinical trial in Q2 of 2025. Pending positive results from those trials, the company plans to resubmit the NDA mid-year 2025.
References
Aldeyra Therapeutics receives complete response letter from the U.S. Food and Drug Administration for the reproxalap new drug application for the treatment of signs and symptoms of dry eye disease. Published April 3, 2025. Accessed April 3, 2025. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-receives-complete-response-letter-us-food-0
Hutton D. Aldeyra Therapeutics receives complete response letter from FDA for reproxalap NDA. Ophthalmology Times. Published November 29, 2023. Accessed April 3, 2025. https://www.ophthalmologytimes.com/view/aldeyra-therapeutics-receives-complete-response-letter-from-fda-for-reproxalap-nda
Harp M. Maharjan E K. FDA accepts NDA from Aldeyra Therapeutics for reproxalap for dry eye. Published November 19, 2025. Accessed April 3, 2025. https://www.ophthalmologytimes.com/view/fda-accepts-nda-from-aldeyra-therapeutics-for-reproxalap-for-dry-eye
