FDA Sets Review Date for Resubmitted Reproxalap in Dry Eye Disease

The FDA has accepted for review the resubmitted new drug application (NDA) for reproxalap and assigned a Prescription Drug User Fee Act (PDUFA) date of April 2, 2025. Developed by Aldeyra Therapeutics, reproxalap is a therapy to treat patients with the signs and symptoms of dry eye disease.

About 39 million people in the United States suffer from dry eye disease, which is characterized by insufficient eye moisture and lubrication. Symptoms include inflammation, pain, a gritty sensation in the eyes and a diminished quality of life. In severe cases it can lead to permanent vision impairment.

Reproxalap is a first-in-class small-molecule modulator of RASP (reactive aldehyde species), which causes inflammation by damaging the tear lipids that maintain the eye moisture barrier. When the barrier is damaged, the eyes can become dry, leading to dry eye disease.

Aldeyra’s original NDA submission was rejected by the FDA in a complete response letter in November 2023 that cited a lack of supporting evidence for reproxalap’s efficacy and requested an additional study with positive results.

The company resubmitted its NDA in October 2024 with results from phase 3 trial, which showed that reproxalap achieved the primary endpoint of reduction of ocular discomfort.

During the trial, 132 participants were treated with reproxalap or vehicle (the drug product without the active ingredient) after exposure to a dry eye chamber, which controls temperature, humidity and air flow. Dry eye chambers have been used in studies to simulate the effect of airplane cabins on contact lens wearers. Primary endpoint was ocular discomfort from 80 to 100 minutes in the dry eye chamber.

Reproxalap has now been studied in more than 2,500 patients. Consistent with prior clinical trials, the most commonly reported adverse event was mild and transient instillation site discomfort. No treatment-related discontinuations were reported.

Aldeyra has an option agreement with AbbVie for the commercialization of reproxalap in which, if exercised, AbbVie will contribute toward commercialization activities.

Aldeyra has also conducted a phase 3 trial of reproxalap to treat patients with allergic conjunctivitis. In this trial, 95 patients were randomly assigned to receive 0.25% reproxalap ophthalmic solution or vehicle, followed by a two-week washout period before crossing over to the other test article.

This trial found that reproxalap resulted in decreased ocular symptoms and redness in patients with allergic conjunctivitis. No serious or severe treatment-emergent adverse events (TEAEs) were reported. The most commonly reported adverse events was mild and included site irritation. Results from this trial were published in December 2023.