On March 17, 2026, the FDA issued a Complete Response Letter (CRL) to Aldeyra Therapeutics for the New Drug Application (NDA) of reproxalap for the treatment of dry eye disease.[3][4] The CRL cites a lack of substantial evidence from adequate and well-controlled studies to demonstrate the drug's effectiveness in treating the signs and symptoms of dry eye.[2][3][4] The inconsistency of study results casts serious doubt on the reliability and significance of the positive findings, while the overall body of evidence from completed clinical trials does not support the product's efficacy.[3][4][5] No safety or manufacturing issues were identified, similar to previous reviews.[3][4] This is the second such letter in 2026 and the third overall, with the previous one from April 2025 also stating a failure to demonstrate effectiveness.[3][6] The FDA recommended investigating the reasons for failure in some studies and identifying patients or conditions where reproxalap may work, without proposing further clinical trials.[4][5] Aldeyra plans to request a Type A meeting with the FDA within 30 days to clarify the steps for NDA approval.[3][4]