Aldeyra Submits NDA for the Novel Dry Eye Therapy Reproxalap

Aldeyra Therapeutics has submitted a new drug application (NDA) to the FDA for topical ocular reproxalap to treat patients with the signs and symptoms of dry eye disease. 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.

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.

The submission is supported by safety and efficacy data from five clinical trials encompassing data for ocular dryness symptom score, ocular redness, Schirmer test, and Schirmer test ≥10 mm responder analysis. 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 dry eye disease objective sign most commonly used for drug approval.

Cathleen McCabe, M.D.

“Schirmer test is an accepted method for measuring tear production and has been used in clinical studies for over 20 years,” Cathleen McCabe, M.D., a dry eye disease specialist for The Eye Associates in Sarasota, Florida and chief medical officer at Eye Health America, said in a press release at the time. “I am extremely encouraged about the Schirmer test results and the other clinical sign endpoint data produced by reproxalap, highlighting the broad therapeutic benefit this therapy may bring to patients suffering from dry eye disease.”

In July, Aldeyra released results of a vehicle-controlled crossover clinical trial. Reproxalap was statistically superior to vehicle for each of the two prespecified primary endpoints, ocular redness in a dry eye chamber and Schirmer test, a measure of tear production, after a single day of dosing. The secondary endpoint of Schirmer test ≥10 mm responder analysis was also achieved. Statistically significant reduction in ocular redness was observed following treatment with reproxalap as soon as 10 minutes. Schirmer test, which was assessed about 10 minutes before and after the fourth dose was statistically significant in favor of reproxalap at both time points. No safety signals were observed in the trial, and reproxalap was well tolerated; there were no treatment-emergent moderate or serious adverse events.

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.