Aldeyra's Reproxalap Eases Eye Discomfort in New Phase 3 Study Despite FDA Rejection

After experiencing a setback last year with the FDA's rejection, Aldeyra Therapeutics has made significant progress with its dry eye drug, reproxalap. In a new phase 3 clinical trial, reproxalap demonstrated a noteworthy reduction in ocular discomfort among participants. This investigational drug was tested on 132 patients who were exposed to a controlled dry eye chamber. The primary goal of the trial was met, showing statistical superiority in reducing ocular discomfort when compared to a vehicle solution, which is the drug product without the active ingredient. The trial’s findings were released on August 8.

Ocular discomfort, also referred to as eye pain, is an FDA-recognized symptom of dry eye disease. Aldeyra’s President and CEO, Todd Brady, M.D., Ph.D., remarked that these results are the first positive phase 3 clinical trial in a dry eye chamber with a symptom-focused primary endpoint. He believes the findings underscore the potential rapid clinical effectiveness of reproxalap in alleviating ocular discomfort associated with dry eye disease. Importantly, no safety issues were identified, and reproxalap was well-tolerated by the patients.

Near the end of the previous year, the FDA had rejected Aldeyra’s initial request for approval of reproxalap, citing inadequate demonstration of "efficacy in treating ocular symptoms associated with dry eyes." The FDA indicated that efficacy could be proven through two symptom trials and two sign trials. At that time, Aldeyra had conducted two trials focusing on ocular redness and another on dry eye disease symptoms. The company subsequently submitted a special protocol assessment to the FDA on November 16, seeking approval for a new dry eye disease chamber crossover clinical trial.

In the complete response letter, the FDA stated that Aldeyra needed to conduct "at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye" before resubmitting for approval. The FDA provided feedback on the new clinical trial protocol and statistical plan, which Aldeyra incorporated into the current trial design.

Participants in the recent trial received reproxalap or a vehicle solution before and during their exposure to the dry eye chamber. Aldeyra believes this approach aligns with the FDA’s draft guidance for dry eye disease. The company, based in Lexington, Massachusetts, now plans to refile for FDA approval later this year, with the review period anticipated to last six months.

Reproxalap's development has encountered multiple challenges. In late 2021, a phase 3 study failed to meet its primary objective of improving ocular redness. The company then shifted its focus to tear production, achieving success in June 2022, which formed the basis for Aldeyra's initial approval request. Additionally, reproxalap is being developed for allergic conjunctivitis, or eye allergies. In June 2023, the drug showed a statistically significant reduction in eye itchiness in a phase 3 trial. Before the rejection of reproxalap for dry eye disease, Aldeyra had intended to discuss a new drug application for conjunctivitis with the FDA in the first half of 2024.

Despite these hurdles, AbbVie has recognized the potential of reproxalap. In November 2023, AbbVie secured an exclusive option to develop, manufacture, and commercialize the drug, in a deal valued up to $300 million, including a $100 million milestone payment contingent on FDA approval for dry eye disease. Aldeyra’s stock has seen a 14% rise, reaching $3.70 per share as of 10:30 a.m. ET today.