Novel Dry Eye Therapy Nears FDA Submission

A new first-in-class therapy that is could be submitted to the FDA later this year could signal a new way to treat dry eye disease. Reproxalap, developed by Aldeyra Therapeutics, is a modulator of RASP, a novel anti-inflammatory target for dry eye. A Type B pre-NDA meeting is expected to be held with the FDA in the third quarter of 2022, followed by a potential NDA submission.

RASP (reactive aldehyde species) binds to cellular biomolecules, disrupting their function and activating pro-inflammatory mediators. RASP have been observed to be elevated in ocular and systemic inflammatory diseases.

Reproxalap is a small molecule that reduces excessive RASP levels. Several clinical trials have shown reproxalap demonstrated consistent statistically significant and clinically relevant activity and has the potential for early and broad activity in dry eye disease.

Data from the phase 3 TRANQUILITY-2 clinical trial show that reproxalap was found to be statistically superior to vehicle for each of the two prespecified primary endpoints, including the Schirmer test and the ³10 mm Schirmer Test Responder Analysis, which are measures of ocular tear production.

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.

Aldeyra intends to submit to the FDA two completed 12-week symptom trials that assess patient-reported ocular dryness score as a primary endpoint, as well as two dry eye chamber trials with ocular redness as the primary endpoint. Ocular redness is an FDA-recognized sign of dry eye disease.

Additionally, the company has completed enrollment in an ongoing 12-month safety trial, and results from a dry eye chamber crossover trial. The results are expected in the third quarter of 2022. Pending the results, the crossover trial is intended to be submitted to the NDA as a supportive trial.

“Many of my dry eye disease patients complain that current treatments take too long to work, prolonging symptoms and negatively affecting quality of life,” Jacob R. Lang, O.D., F.A.A.O., a dry eye disease specialist for Associated Eye Care in St. Paul, Minnesota, said in a press release. “Based on its rapid symptomatic control demonstrated across multiple clinical trials, reproxalap has the potential to be not only an important treatment option but a first-line therapy for 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.

Aldeyra is also conducting phase 3 trial of reproxalap to treat allergic conjunctivitis. About 100 million patients in the United States have allergic conjunctivitis. Company officials estimate that up to 30 million of these patients either don’t respond adequately to, or are dissatisfied with, topical antihistamines, the current standard of care. Histamine, they said, is only one of the biological mediators of allergic conjunctivitis.