The FDA has delayed an approval decision for Aldeyra Therapeutics’ lead dry eye disease candidate, adding another detour to the candidate’s winding road to potentially enter the market.
At a Dec. 12 meeting, the agency requested Aldeyra submit a report for a failed trial that the regulator had previously told the company not to include in reproxalap’s new drug application, Aldeyra CEO Todd Brady, M.D., Ph.D., explained during a Dec. 16 conference call.
Upon receiving that clinical data report, the FDA pushed back the Prescription Drug User Fee Act (PDUFA) target action date from Dec. 16 to March 16, 2026.
When reached for comment, Andrew Nixon, communications director for the Department of Health and Human Services, which oversees the FDA, told Fierce that “information about potential or pending applications is confidential.”
Reproxalap, a small molecule that binds reactive aldehyde species, has previously been rejected twice by the FDA, with the most recent rebuff occurring this April. At the time, the agency said there wasn't enough data showing the molecule’s ability to address the symptoms of dry eye, and requested another trial demonstrating efficacy.
Aldeyra appeared to meet the mark in May, reporting that reproxalap had hit the primary endpoint in a phase 3 trial by significantly improving eye discomfort compared with the placebo. In that trial, patients were tested in a chamber designed to induce symptoms.
At the same time, however, the biotech announced that a separate field trial of the potential treatment had failed to meet its primary endpoint, but was “numerically supportive of reproxalap and consistent with prior field trials.”
“In June, the field trial was specifically discussed with the FDA, and [a] written agreement was reached not to submit the trial to the NDA,” Brady explained. Though this goes against FDA guidance to submit all clinical trials to the agency when seeking approval, the CEO acknowledged, the biotech’s conversations with the FDA’s Division of Ophthalmology centered around addressing the complete response letter, which sought one trial showing the therapeutic's ability to improve symptoms.
“We were quite clear with the division that the field trial, while supportive of reproxalap, did not meet statistical significance,” Brady added. “And at that time, the division agreed in writing that only the chamber trials need to be submitted.”
Aldeyra submitted the single successful trial to the FDA over the summer and the agency accepted the resubmitted NDA for review on July 17, according to a release from the biotech. The regulator sent a draft label for reproxalap to the company in early December, Brady said, and Aldeyra responded with comments.
Though not part of the NDA, a report of the field trial was also submitted to the agency through a different pathway—reproxalap’s investigational new drug application. In this sense, the FDA already had, and likely already reviewed, the report that it was now requesting, Brady said.
“It seems that the review itself is substantively complete,” he said. “What appears to have happened is that the director of the Office of Specialty Medicine decided that the protocol should be followed in the standard sense that all completed trials should be submitted to the NDA.”
The Office of Specialty Medicine (OSM) oversees the Division of Ophthalmology, and Brady said that Aldeyra has had no interaction with OSM or any other part of the FDA aside from the ophthalmology office. The request to submit a report on the failed trial to the NDA, which triggered the PDUFA delay, was made by the OSM, he explained.
Extensive layoffs and leadership flux at the FDA this year has prompted fears of disrupted drug reviews and the loss of American biotech leadership. Brady said Aldeyra has seen no turnover in the ophthalmology staff that they interact with. The only major change, he noted, is that the former director of OSM retired over the summer, with a new director taking over.
It was not immediately clear who the current director of OSM is—an FDA webpage last updated in 2020 lists Charles Ganley, M.D., as acting director. At the time of publication, the FDA had not answered questions from Fierce about leadership at OSM.
The FDA delay doesn't impact an exclusive option agreement that Aldeyra entered into with AbbVie in November 2023, biotech CEO Brady added. If the FDA approves reproxalap, AbbVie is on the line to pay Aldeyra a $100 million milestone payment. Under the terms of that deal, AbbVie will then have 10 business days after reproxalap is approved to decide whether or not to exercise its option to license the drug.