FDA CRL - Aldeyra Therapeutics, Inc.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter to Aldeyra Therapeutics, Inc. for its New Drug Application (NDA 216442) for Reproxalap Ophthalmic Solution on April 2, 2025. The FDA concluded that the application, in its current form, cannot be approved due to a lack of substantial evidence demonstrating the drug's efficacy, as defined under 21 CFR 314.126.

The primary issue is the failure to show efficacy in adequate and well-controlled studies for treating ocular symptoms associated with dry eyes. The FDA identified significant concerns with the data interpretation and methodology of Study 030. Specific problems included analytical challenges from comparing Visit 2 and Visit 4 data, issues with baseline differences influencing mean VAS scores, and inconsistencies when compared to previous studies. The FDA also noted that proposed statistical models did not adequately account for baseline differences, deeming the study's primary efficacy endpoint analysis problematic and not robust, and that it failed to achieve statistical significance under alternative analyses.

To address these deficiencies, Aldeyra Therapeutics must conduct at least one additional adequate and well-controlled study demonstrating a positive effect on dry eye symptoms. Any changes to the study protocol or statistical analysis plan after patient enrollment will require prior FDA agreement. The company is also required to submit a safety update and resubmit the proposed proprietary name once all application deficiencies are resolved. Aldeyra has one year to resubmit the application or pursue other available actions.