Aldeyra anticipates FDA rejection of dry eye drug following regulatory meeting

Aldeyra anticipates FDA rejection of dry eye drug following regulatory meeting

Published: Oct 17, 2023

By Tristan Manalac


Aldeyra Therapeutics on Monday announced in an SEC filing that the FDA is likely to reject its New Drug Application for reproxalap for the treatment of dry eye disease.

This follows a late-cycle review meeting in which the regulator flagged “substantive review issues” with the New Drug Application (NDA). The FDA pointed out to Aldeyra that it does not appear to “have data to support the clinical relevance of the ocular signs to support your dry eye indication,” according to the company’s SEC filing.

Aldeyra has since responded to the regulator and provided additional information that the company contends is enough to address the FDA’s concerns with the NDA.

However, so far, the FDA “has not directly opined on the sufficiency of the information submitted, has no legal obligation to review the information submitted by Aldeyra, and has indicated that Aldeyra needs to conduct an additional clinical trial to satisfy efficacy requirements,” the company’s SEC filing states.

Reproxalap is a novel small-molecule drug candidate that covalently binds to and inhibits reactive aldehyde species (RASP), which typically spikes in concentration during inflammatory episodes in the eye. In December 2021, the investigational ophthalmic solution returned mixed results in the Phase III TRANQUILITY trial.

The treatment led to significant improvements in the Schirmer test, which assesses whether the eyes can produce enough tears or not—a key secondary endpoint of the study. However, the candidate missed its primary endpoint of ocular redness.

In a subsequent Phase III trial, dubbed TRANQUILITY-2, Aldeyra dropped ocular redness as a key metric of efficacy and instead relied on the Schirmer test and a responder analysis. TRANQUILITY-2 met both of these primary endpoints in June 2022 and at the time, CEO Todd Brady said that the study’s results “are expected to complete the most comprehensive dry eye disease NDA submission to date.”

The FDA accepted the NDA in February 2023 and indicated that it did not plan to hold an advisory committee meeting. The target action date is on Nov. 23. In its SEC filing on Monday, Aldeyra said that the regulator “may not be in the position to approve the NDA for reproxalap” by this deadline.

The company also said Monday that in case the FDA does not approve reproxalap, or if the approval is delayed or limited, “Aldeyra’s ability to generate revenue will be significantly delayed.”

If the FDA does indeed deny reproxalap’s NDA, the RASP inhibitor will be Aldeyra’s second rejected candidate in recent months. In June 2023, the regulator likewise blocked ADX-2191 (methotrexate injection, USP), which the company was proposing as a treatment for primary vitreoretinal lymphoma.

The regulator cited the lack of data and well-controlled supporting studies in its Complete Response Letter.

Source: BioSpace