Aldeyra Therapeutics announced on March 17 that the U.S. Food and Drug Administration (FDA) has rejected its lead drug candidate, reproxalap, for the treatment of dry eye disease for a third time. The decision was delivered in a complete response letter from the FDA, which cited insufficient evidence from well-controlled studies to support the drug's efficacy.
The repeated rejections are significant because they highlight ongoing challenges in developing new treatments for dry eye disease, a condition affecting millions worldwide. Aldeyra’s stock price dropped more than 70% to $1.25 per share following the announcement.
According to Aldeyra, the FDA stated there was “a lack of substantial evidence consisting of adequate and well-controlled investigations” that reproxalap “will have the effect it purports.” The agency also noted an “inconsistency of study results” and said that Aldeyra’s application “failed to demonstrate efficacy in adequate and well controlled studies in the treatment of signs and symptoms of dry eye disease.” No safety or manufacturing concerns were identified by regulators.
Reproxalap has faced regulatory hurdles since its first rejection in November 2023 due to questions about its effectiveness. A second rejection followed in April last year, again over efficacy concerns. A Phase 3 trial conducted in December 2021 showed mixed results: while there were improvements in tear production—a secondary endpoint—the primary outcome related to ocular redness was not met. Aldeyra resubmitted its application with additional data from a dry eye chamber study in June 2025, but this did not satisfy FDA requirements.
Despite these setbacks, CEO Todd Brady said Aldeyra will continue efforts to gain approval for reproxalap. “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 to what is, to our knowledge, the only drug with clinical activity within minutes of administration in patients with dry eye disease,” he said.
Aldeyra plans to request a Type A meeting with the FDA to determine next steps toward potential approval. As of December 2025, Aldeyra reported having $70 million in cash and equivalents—funds expected to support operations into 2028.
