FDA Once Again Rejects Aldeyra's NDA of Reproxalap for Dry Eye Disease
The FDA issued a complete response letter declining to approve Aldeyra Therapeutics' resubmitted 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 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. According to Aldeyra, 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 two symptom trials and two sign trials. Among other clinical trials of reproxalap, Aldeyra previously conducted two 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. In November 2023, the FDA issued a complete response letter to the initial NDA stating that at least one additional symptom trial was required. Following discussions with the FDA, and as part of a strategy designed to account for disease heterogeneity and potential differences in clinical sites and environment, Aldeyra initiated three 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.
Aldeyra 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 expects to announce topline 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 said it intends to resubmit the NDA mid-year 2025. The review period for the potential NDA resubmission is expected to be 6 months.
As of December 31, 2024, Aldeyra reported cash, cash equivalents, and marketable securities of $101 million. With a majority of costs for the ongoing dry eye clinical trials having occurred in 2024, the full-year 2025 costs of the trials are expected to be approximately $6 million.
“Pending positive results from the ongoing clinical trials and discussions with the FDA, we look forward to a potential NDA resubmission mid-year 2025,” Todd C. Brady, MD, PhD, President and Chief Executive Officer of Aldeyra Therapeutics, said in a company news 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.”