FDA Requests Further Study on Aldeyra Therapeutics’ Reproxalap for DED

Aldeyra Therapeutics announced the receipt of a Complete Response Letter from the U.S. Food and Drug Administration (FDA) in response to the New Drug Application (NDA) for reproxalap, an investigational drug candidate designed for the treatment of dry eye disease.

While the FDA's letter highlighted that there were no identified safety or manufacturing issues with reproxalap, it expressed that the NDA fell short of demonstrating "efficacy in treating ocular symptoms associated with dry eyes." The agency suggested that "at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye" should be conducted.

In adherence to the FDA's guidance on dry eye disease, which suggests demonstrating efficacy through two symptom trials and two sign trials, Aldeyra had previously conducted two trials focused on ocular redness (a dry eye disease sign) and a dry eye disease symptom trial. On November 16, 2023, Aldeyra submitted a Special Protocol Assessment (SPA) for a dry eye disease chamber crossover clinical trial (the proposed trial), similar to the crossover chamber trial whose results were announced on July 12, 2022. The SPA review cycle is expected to take 45 days, with Aldeyra anticipating FDA feedback on the SPA in December 2023. The proposed trial, projected to cost less than $2 million, is expected to yield top-line results in the first half of 2024, contingent upon FDA feedback on the SPA.

Pending positive outcomes from the proposed trial and FDA SPA feedback, Aldeyra anticipates the potential resubmission of the NDA in the first half of 2024. The company aims to incorporate in the potential NDA resubmission a draft label outlining chronic and acute symptomatic benefits, along with the acute reduction in ocular redness attributed to reproxalap. The review period for the potential NDA resubmission is estimated to span six months.

"With $143 million in cash, cash equivalents, and marketable securities as of September 30, 2023, we are well positioned to conduct another symptom trial of reproxalap in patients with dry eye disease, with a potential NDA resubmission in the first half of 2024," stated Todd C. Brady, M.D., Ph.D., President and Chief Executive Officer of Aldeyra Therapeutics. "If the SPA and proposed trial results are successful, and the potential resubmitted NDA is approved, the drug label may be the first label in dry eye disease to contain acute reduction in ocular redness, as well as a combination of chronic and acute symptomatic benefit, potentially highlighting the rapid activity of reproxalap on both signs and symptoms of dry eye disease."

Reproxalap is currently in development for the treatment of allergic conjunctivitis, a common inflammatory disease impacting approximately 20% of the global population. The results from the third positive Phase 3 clinical trial of reproxalap in allergic conjunctivitis, known as the INVIGORATE-2 Trial, were disclosed on June 15, 2023.

 Aldeyra has plans to hold a Type C meeting with the FDA in the first half of 2024 to initiate discussions regarding the potential New Drug Application (NDA) submission of reproxalap specifically for the treatment of allergic conjunctivitis.

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