Aldeyra Therapeutics has received a setback in its efforts to bring a new treatment for dry eye disease to market, following a Complete Response Letter (CRL) issued by the U.S. Food and Drug Administration (FDA). The agency declined approval of the company’s New Drug Application (NDA) for reproxalap, citing insufficient evidence of the drug’s effectiveness.
According to the FDA, the application failed to demonstrate “substantial evidence” of efficacy based on adequate and well-controlled clinical trials. The agency highlighted inconsistencies in study results, raising concerns about the reliability and clinical relevance of positive findings. Ultimately, the FDA concluded that the totality of evidence from completed trials does not support the drug’s effectiveness in treating both the signs and symptoms of dry eye disease.
Despite these concerns, the FDA did not identify any issues related to safety or manufacturing, consistent with previous reviews of reproxalap. This distinction suggests that while the drug appears to meet safety standards, its therapeutic benefit remains unproven under current data.
During the review process, draft labeling was shared with Aldeyra in December 2025 and again in March 2026. However, the company noted that label discussions were not finalized, indicating that the regulatory process was still ongoing prior to the CRL issuance.
In its response, the FDA recommended that Aldeyra further investigate the reasons behind the failed trials and identify specific patient populations or conditions where reproxalap may demonstrate clearer benefits. Notably, the agency did not request additional clinical trials or new confirmatory studies at this stage.
Aldeyra stated that it does not plan to initiate new trials but will instead seek a Type A meeting with the FDA to clarify the path forward for potential approval. Under Prescription Drug User Fee Act (PDUFA) guidelines, such meetings are typically scheduled within 30 days of request submission.
Company CEO Dr. Todd C. Brady emphasized the urgency of addressing the FDA’s concerns, particularly given the unmet need in dry eye disease treatment. He highlighted reproxalap’s rapid onset of action, which the company believes differentiates it from existing therapies that may take weeks or months to show improvement.
As of the end of 2025, Aldeyra reported $70 million in cash and marketable securities, which it expects will sustain operations through 2028 while it navigates the regulatory pathway for reproxalap.