Aldeyra Therapeutics (NASDAQ:ALDX) said it plans to submit a formal dispute resolution request, or FDRR, to the FDA’s Office of New Drugs seeking review of the agency’s latest complete response letter for reproxalap, its investigational treatment for the signs and symptoms of dry eye disease.
The company announced the planned appeal during a regulatory update call on Sept. 29. President and Chief Executive Officer Todd Brady said the FDRR will challenge the FDA’s conclusion that the totality of clinical evidence does not support reproxalap’s effectiveness.
Regulatory History
Aldeyra initially submitted a new drug application, or NDA, for reproxalap in November 2022. The company said the filing included six adequate and well-controlled trials that it believes demonstrated improvement in dry-eye symptoms as well as tear production, measured by the Schirmer test, and ocular redness.
The FDA issued a complete response letter in November 2023 recommending an additional symptom trial. Aldeyra subsequently initiated three symptom-focused studies, including a six-week field trial and two dry-eye chamber trials conducted under controlled environmental conditions.
According to Brady, the first dry-eye chamber study met its primary endpoint, and Aldeyra resubmitted its NDA in October 2024. The FDA again issued a complete response letter in April 2025 recommending another symptom trial. After two ongoing studies were completed, Aldeyra said it reached agreement with the FDA to submit the positive chamber trial and resubmitted the NDA in June 2025.
The agency later requested the field-trial results, which the company said constituted a major amendment and resulted in a three-month delay to the review timeline. On March 16, 2026, the FDA issued another complete response letter. Brady said that letter did not request further trials and did not identify manufacturing or safety issues, but stated that the totality of evidence did not support the product’s effectiveness.
Company’s Case for Reproxalap
Brady said Aldeyra has submitted nine clinical trials and believes the data package represents the largest and most comprehensive set of clinical studies submitted in a dry-eye-disease NDA. The company maintains that its results support reproxalap’s activity across dry-eye symptoms, tear production and ocular redness.
Aldeyra argued that dry-eye studies can be difficult to interpret because symptoms and environmental conditions vary considerably. Brady said humidity, temperature, wind, particulate matter and other factors can affect trial outcomes, especially in geographically dispersed field studies. He said controlled, single-site dry-eye chamber studies may be better positioned to identify treatment effects during acute disease exacerbations.
The company said it believes its data meet recommendations in draft FDA dry-eye guidance, including possible pathways involving two positive Schirmer-response studies or two positive symptom studies and two positive sign studies. Aldeyra also cited its view that the statutory standard for substantial evidence can be satisfied through more than one adequate and well-controlled trial, or one such trial with confirmatory evidence.
Brady said the FDRR will also discuss the reasons certain studies may not have achieved statistical significance, including environmental and day-to-day variability in dry-eye symptoms.
Expected Appeal Timeline
Under PDUFA goals, an FDRR-related meeting should generally be handled as a Type A meeting and occur within 30 days of submission, Aldeyra said. A decision is generally expected within 30 days after that meeting, although the process could take longer if the deciding official seeks more information, additional discussions, expert input or an advisory committee.
Aldeyra expects to meet with the FDA’s Office of New Drugs during the fourth quarter of 2026. Following an FDRR decision, the company said the NDA would need to be resubmitted with any additional information required by the agency.
Brady said Aldeyra is aware of two FDRRs submitted in 2026 following Division of Ophthalmology reviews. One resulted in an appeal-granted decision about 60 days after submission, while another remains pending an advisory panel. He said Aldeyra does not view an advisory committee as likely in dry eye disease, citing the condition’s established treatment landscape, though he acknowledged that additional internal or external review remains possible.
Cash Runway and Pipeline Changes
Aldeyra reported $45.1 million in cash equivalents and marketable securities as of June 30, 2026. The company updated its guidance to say its existing resources are expected to fund operations into 2029. That estimate excludes potential partnership or product revenue from reproxalap, including revenue associated with Aldeyra’s previously disclosed option agreement with AbbVie.
The company said its budget includes continued advancement of its primary vitreoretinal lymphoma pivotal program and contingency funding for potential additional dry-eye clinical work if needed.
To conserve resources, Aldeyra said it is suspending development of ADX-2191 in retinitis pigmentosa. Brady said the company’s oral RASP inhibitor, ADX-248, has completed Phase 1 testing and is ready for Phase 2 development. Guidance on ADX-248 and ADX-246 is expected after the reproxalap FDRR is resolved.
About Aldeyra Therapeutics (NASDAQ:ALDX)
Aldeyra Therapeutics, Inc is a clinical-stage biotechnology company focused on developing therapies for immune-mediated diseases. The company’s research centers on reactive aldehyde species, or RASP, which are inflammatory mediators that can contribute to tissue damage and disease progression.
Aldeyra’s lead investigational product is reproxalap, a small-molecule RASP inhibitor being developed for ocular conditions, including dry eye disease and allergic conjunctivitis. The company has also developed ADX-2191, an investigational intravitreal formulation of methotrexate intended for the treatment of certain rare retinal diseases, including proliferative vitreoretinopathy and retinitis pigmentosa.
Founded in 2008 and headquartered in Lexington, Massachusetts, Aldeyra conducts its research and clinical development activities primarily in the United States.
