FDA Sets PDUFA Date for Dry Eye Disease Drug

The FDA has accepted the new drug application (NDA) for topical ocular reproxalap, a first-in-class drug to treat patients with the signs and symptoms of dry eye disease. The FDA assigned a Prescription Drug User Fee Act (PDUFA) date of Nov. 23, 2023.

Dry eye disease is a common inflammatory disease estimated to affect 39 million or more adults in the United States. The disease is characterized by insufficient moisture and lubrication in the anterior surface of the eye, leading to dryness, inflammation, pain, discomfort, irritation, diminished quality of life, and in severe cases, permanent vision impairment.

Developed by Aldeyra Therapeutics, reproxalap is a first-in-class small-molecule modulator of RASP (reactive aldehyde species), which are elevated in ocular and systemic inflammatory disease. In patients with dry eye disease, RASP may contribute to ocular inflammation and changes in tear lipid composition.

Related: Aldeyra Submits NDA for the Novel Dry Eye Therapy Reproxalap

The NDA is supported by safety and efficacy results from five clinical trials encompassing data for ocular dryness symptom score, ocular redness, Schirmer test, and Schirmer test ≥10 mm responder analysis. The NDA includes activity ranging from within minutes of drug administration to up to 12 weeks of treatment, crossover and parallel-group clinical trial designs, and assessment in dry eye chamber challenge and natural environment settings.

Results of the phase 3 TRANQUILITY-2 trial, which were released in June 2022, showed that reproxalap was statistically superior to vehicle for each of the two prespecified primary endpoints, Schirmer test and ≥10 mm Schirmer test responder proportions after a single day of dosing. The Schirmer test, a measure of ocular tear production, is the objective sign most commonly used for drug approval for dry eye disease.

Topical ocular reproxalap has been studied in more than 2,000 patients with no observed clinically significant safety concerns; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials.

In addition to dry eye disease, reproxalap is in late-stage development for allergic conjunctivitis, a condition that is commonly associated with dry eye disease. Results of the phase 3 INVIGORATE-2 trial are expected in 2023.