In its complete response letter, the FDA said Aldeyra had failed to demonstrate reproxalap’s efficacy in adequate and well-controlled studies. The FDA previously turned the candidate away in November 2023 and April 2025.
After three strikes, is Aldeyra Therapeutics out in dry eye disease? On Tuesday, the FDA again turned away the company’s lead drug candidate reproxalap, adding another chapter to a regulatory saga that includes two other rejections over the past two and a half years.
In its complete response letter (CRL), the FDA described “a lack of substantial evidence consisting of adequate and well-controlled investigations” that reproxalap “will have the effect it purports,” according to Aldeyra’s press release on Tuesday. Aldeyra’s application also “failed to demonstrate efficacy in adequate and well controlled studies in the treatment of signs and symptoms of dry eye disease,” and there was an “inconsistency of study results,’” the FDA added, per Aldeyra. No safety or manufacturing concerns were identified.
Aldeyra’s stock was down more than 70% to $1.25 per share at the opening bell on Tuesday.
Reproxalap has traversed a bumpy regulatory road. The candidate was first rejected in November 2023, with the FDA arguing that Aldeyra had failed to sufficiently establish efficacy for ocular symptoms in dry eye disease. Reproxalap was turned away again in April last year, with the FDA again raising questions over efficacy.
Indeed, a Phase 3 trial of reproxalap had returned mixed results in December 2021, showing significant improvements in tear production, a key secondary endpoint, but missing the primary outcome of ocular redness.
The company filed a resubmission in June 2025—which the FDA accepted in July—including additional data from a dry eye chamber study. While that study showed significantly improved ocular discomfort versus vehicle, it clearly wasn’t enough for the FDA.
In the most recent CRL, the agency did not recommend that Aldeyra conduct additional trials of reproxalap nor request additional confirmatory evidence. In response, the biotech plans to “expeditiously request” a Type A meeting to understand the actions it must take to obtain approval for the drug.
Aldeyra CEO Todd Brady emphasized that the company has no plans to give up on 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 in a statement.
Adding to the friction surrounding reproxalap is a risk statement added by Aldeyra to a quarterly filing document last November, alerting shareholders that “short sellers may be manipulative and may drive down the price of our common shares.”
As of December 2025, Aldeyra had cash, cash equivalents and marketable securities of $70 million, according to Tuesday’s announcement, a tally the company expects to support operations into 2028.
