Aldeyra Therapeutics announced receipt of a Complete Response Letter from the US Food and Drug Administration (FDA) for the resubmission of the new drug application (NDA) of reproxalap, an investigational drug candidate, for the treatment of dry eye disease.

Although no manufacturing or safety issues with reproxalap were identified, the company said in a press release that the FDA stated in the letter 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. 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.

Per draft FDA dry eye disease guidance, to be considered for regulatory approval in the United States, efficacy in dry eye disease may be demonstrated with 2 symptom trials and 2 sign trials. Among other clinical trials of reproxalap, Aldeyra previously conducted 2 trials for ocular redness (a dry eye disease sign) in a dry eye chamber, and 2 dry eye disease symptom field (environmental exposure) trials, which were submitted as part of an initial NDA in November 2022.

In November 2023, the FDA issued a Complete Response Letter to the initial NDA stating that at least 1 additional symptom trial was required. Following discussions with the FDA, and as part of a comprehensive strategy designed to account for disease heterogeneity and potential differences in clinical sites and environment, Aldeyra initiated 3 clinical trials assessing dry eye disease symptoms: a dry eye chamber trial, a clinical trial in a different dry eye chamber, and a 6-week field trial.

In August 2024, Aldeyra announced the achievement of the primary endpoint in the first dry eye chamber clinical trial of reproxalap, and the NDA was resubmitted in October 2024. The company said a Type A meeting is expected to be held within approximately 30 days to discuss the Complete Response Letter for the resubmitted NDA and the ongoing clinical trials of reproxalap in dry eye disease.

In the second quarter of 2025, Aldeyra said it expects to announce top-line results from the ongoing dry eye disease field trial and the ongoing chamber clinical trial. Subject to positive results and discussions with the FDA, Aldeyra intends to resubmit the NDA mid-year 2025. The review period for the potential NDA resubmission is expected to be 6 months, the company said. 

“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 Todd C. Brady, MD, PhD, president and chief executive officer of Aldeyra Therapeutics, in the press release. “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.”