Aldeyra awaits FDA feedback after third reproxalap rejection

Aldeyra Therapeutics awaits FDA feedback on its dry eye drug reproxalap after a third Complete Response Letter questioned the totality of evidence.

Aldeyra Therapeutics has received three Complete Response Letters from the FDA for reproxalap, its lead dry eye candidate, with the latest rejection questioning whether the company had demonstrated sufficient evidence for approval.

"The latest CRL didn't say run more trials. It said prove totality," Todd Brady, President and Chief Executive Officer of Aldeyra, said at the Jefferies Global Healthcare Conference on June 4.

The FDA identified five trials in the CRL, two of which Aldeyra agrees were not statistically significant. The company disputes the agency's assessment on the remaining three, citing issues including a baseline imbalance in one study. Brady said the company is days away from receiving preliminary FDA comments ahead of a Type A meeting, with minutes expected 30 days after the meeting.

The outcome carries significant financial implications. Aldeyra has a partnership with AbbVie that includes a $200 million upfront payment if the pharma giant opts in after approval, plus additional milestones and a 60-40 profit split. The company reported roughly $50 million in cash after paying down $15 million in debt, providing runway into the second half of 2028.

A Disputed Evidence Package

Brady said the FDA did not request another trial in the March CRL, and division leadership told the company the agency wanted to give Aldeyra the opportunity to demonstrate totality without running a new study. If additional trials are ultimately required, Brady said the strongest results have been on the Schirmer test, which measures tear production. Those studies could be short, two-week or two-dose trials, each costing $5 million or less.

Aldeyra has laid out its trial data and primary endpoints in its corporate deck, including both the company's view and the FDA's view of the results, allowing investors to assess the argument directly.

If the FDA maintains its position, Aldeyra would consider a formal appeal through the Formal Dispute Resolution Request process. Brady said an appeal would go to the Office of New Drugs because the signatory office on the rejection is the Office of Specialty Medicine, above the ophthalmology division.

Beyond Dry Eye — A Broader Pipeline

Aldeyra's pipeline extends beyond reproxalap. The company has an NDA-stage ocular lymphoma asset — an injectable formulation of methotrexate, which is the standard of care but has no approved product for lymphoma in the eye. Aldeyra previously submitted an NDA for the program after FDA encouragement, but the application was rejected. The company is now discussing with the FDA what additional evidence may be needed.

In atopic dermatitis, Aldeyra has an oral RASP inhibitor that recently completed Phase 1 testing, with investors showing interest given unmet need in children and mild disease. The company also hopes to enter the clinic next year for dry age-related macular degeneration, assuming the program progresses as planned.

Aldeyra shares, trading at a market capitalization of roughly $99 million, reflect the binary nature of the reproxalap decision. A positive FDA outcome could unlock the AbbVie partnership and a potential $200 million upfront payment — more than double the company's current market value. A sustained rejection would leave Aldeyra dependent on its earlier-stage pipeline and roughly $50 million in cash, which Brady said provides enough capital to continue the reproxalap regulatory process, potentially run additional dry eye trials, and continue discussions with the FDA on ocular lymphoma. "I don't think from a cash standpoint or an infrastructure standpoint we're at risk of anything in the near term," Brady said.

This article is for informational purposes only and does not constitute investment advice.