FDA Rejects Aldeyra’s Dry Eye Drug, Cites Need for Additional Trial
Pictured: Elderly person using eye drops/iStock, megaflopp
In its Complete Response Letter, the regulator noted that Aldeyra’s New Drug Application (NDA) failed to sufficiently show reproxalap’s “efficacy in treating ocular symptoms associated with dry eyes,” according to the company’s announcement. The FDA is also requesting “at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye.”
The FDA did not identify safety or manufacturing issues with reproxalap, according to the company.
Aldeyra CEO Todd Brady in a statement said that the company is “well positioned to conduct another symptom trial of reproxalap in patients with dry eye disease,” given that it is currently sitting at $143 million in cash, cash equivalents and marketable securities.
Per the FDA’s draft guidance, efficacy in dry eye disease can be established through two symptom trials and two sign trials. Aldeyra previously performed two trials assessing ocular redness, a sign of dry eye disease, as well as one symptom study. In line with the regulator’s requirements, the company has submitted a Special Protocol Assessment for its proposed chamber crossover clinical trial.
Aldeyra is expecting to receive feedback from the FDA in December 2023 and, if the proposed trial is approved, is eyeing top-line data and an NDA resubmission in the first half of 2024. The company estimates that the proposed trial will cost less than $2 million, according to Monday’s announcement.
Reproxalap is a small molecule drug candidate that covalently binds to reactive aldehyde species (RASP), to inhibit their action. RASP levels are typically elevated during inflammatory episodes in the eye.
In December 2021, the Phase III TRANQUILITY trial returned mixed results for reproxalap, which induced significant improvements in tear production, a key secondary endpoint, but missed its primary outcome of ocular redness. Aldeyra then ran another Phase III trial, called TRANQUILITY-2, leaving ocular redness out as a key metric of efficacy.
In June 2022, Aldeyra reported that reproxalap aced TRANQUILITY-2 and that it was preparing an NDA for the drug candidate. At the time, Brady said that data from TRANQUILITY-2 “are expected to complete the most comprehensive dry eye disease NDA submission to date.” The FDA accepted the NDA in February 2023.
However, in October 2023, the FDA indicated to Aldeyra in a late-cycle review meeting that it had found “substantive review issues” with the NDA, pointing out that the biotech did not have sufficient evidence “to support the clinical relevance of the ocular signs to support your dry eye indication.” Aldeyra in an SEC filing told investors that because of these regulatory issues, it was anticipating a rejection for reproxalap.