FDA Issues Third Complete Response Letter to Aldeyra Therapeutics for Dry Eye Drug Reproxalap

In another setback for Aldeyra Therapeutics, the FDA issued a third Complete Response Letter (CRL) regarding its new drug application (NDA) for investigational dry eye treatment reproxalap.

In the letter, the FDA stated that the application failed to provide sufficient evidence of effectiveness. Specifically, the agency cited “a lack of substantial evidence consisting of adequate and well-controlled investigations” demonstrating that reproxalap delivers its intended therapeutic effect. The FDA further concluded that the application “failed to demonstrate efficacy in adequate and well-controlled studies in the treatment of signs and symptoms of dry eye disease.”

Regulators also raised concerns about inconsistencies across clinical trial results, noting that these discrepancies “raise serious concerns about the reliability and meaningfulness of the positive findings.” According to the FDA, the overall body of evidence submitted “does not support the effectiveness of the product.”

The agency did not identify any safety or manufacturing issues—consistent with previous regulatory reviews of reproxalap.

Aldeyra indicated that during the review process, the FDA provided draft labeling in December 2025 and again in March 2026, though the company believes that label negotiations were not finalized prior to the CRL.

The FDA recommended that Aldeyra further investigate the causes of trial failures and identify patient populations or conditions in which reproxalap may demonstrate clearer benefit. Notably, the agency did not request additional confirmatory trials or new clinical studies.

In response, Aldeyra said it does not currently plan to initiate new trials. Instead, the company intends to request 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 a request.

“To the thousands of American and Canadian patients who participated in our clinical trials and to the tens of millions of patients with dry eye disease worldwide, I want to assure you that we will work with urgency to support the FDA in enabling market access,” Todd C. Brady, MD, PhD, President and Chief Executive Officer of Aldeyra, said in a company news release. He added that reproxalap may offer rapid symptom relief, with clinical activity observed within minutes—contrasting with existing treatments that can take weeks or months to show modest improvement.

As of December 31, 2025, Aldeyra reported $70 million in cash, cash equivalents, and marketable securities. The company said it expects this funding to sustain operations through 2028 as it works to address regulatory concerns and determine next steps for reproxalap.

Originally published online on Eyewire.