On April 3, 2025, Aldeyra Therapeutics announced that the U.S. Food and Drug Administration issued a Complete Response Letter for its resubmitted New Drug Application for reproxalap, a novel investigational therapy for the treatment of signs and symptoms of dry eye disease.
The FDA concluded that the Application didn't demonstrate adequate efficacy in the studies conducted thus far and recommended that Aldeyra conduct at least one additional trial focusing on ocular symptoms.
According to a press release from Aldeyra, the Complete Response Letter (CRL) raised concerns regarding data interpretation. Specifically, the FDA cited methodologic issues such as baseline score differences across treatment arms. However, the agency did not identify any manufacturing or safety concerns with reproxalap.
The initial New Drug Application (NDA), which was submitted in November 2022, included data from two dry eye chamber trials that assessed ocular redness in dry eye disease DE), and two field-based symptom trials that assessed ocular symptoms with environmental exposure.
In November 2023, the FDA issued a CRL requesting an additional symptom trial. In response, Aldeyra initiated three more trials “to account for disease heterogeneity and potential differences in clinical sites and environments,” they noted in their press release. The trials included a dry eye chamber trial, a second chamber trial, and a 6-week field trial.
The NDA was resubmitted in October 2024 after reporting achievement of the primary endpoint in the first new chamber trial.
A Type A meeting with the FDA is expected within 30 days to discuss the recent CRL and ongoing clinical trials. Aldeyra plans to announce top-line data from the current field trial and second chamber trial in the second quarter of 2025.
“We look forward to a potential NDA resubmission mid-year 2025, pending positive results from ongoing clinical trials and discussions with the FDA,” said Todd C. Brady, MD, PhD, President and Chief Executive Officer of Aldeyra. He highlighted that “reproxalap remains the only late-stage topical ocular therapy” that is potentially suitable for chronic administration that may reduce both ocular redness and discomfort.
The potential review period following this resubmission is expected to be 6 months.
Reproxalap is a first-in-class, small-molecule reactive aldehyde species modulator that is under investigation for the treatment of dry eye disease and allergic conjunctivitis. To date, it has been studied in more than 2,500 patients, and no significant safety issues have been reported. The most common adverse event has been mild, transient instillation site irritation.
Aldeyra will host a conference call to provide further regulatory updates. Details are available in the press release.