Aldeyra Therapeutics Hits Primary Endpoint in Phase 3 Dry Eye Trial of Reproxalap

Aldeyra Therapeutics, Inc., a biotech firm focused on developing treatments for immune-mediated and metabolic diseases, has announced a significant milestone in the clinical development of its investigational drug candidate, 0.25% reproxalap ophthalmic solution, aimed at treating dry eye disease. The company reported the successful achievement of the primary endpoint in a Phase 3, randomized, double-masked, vehicle-controlled clinical trial conducted in a dry eye chamber.

In this pivotal trial, reproxalap was evaluated against a placebo (vehicle) for its efficacy in reducing ocular discomfort, a symptom recognized by the U.S. Food and Drug Administration (FDA) as a primary endpoint for dry eye disease studies. The results demonstrated that reproxalap significantly outperformed the placebo in alleviating ocular discomfort, with a statistically significant p-value of 0.004.

Dr. Todd C. Brady, President and CEO of Aldeyra, highlighted the groundbreaking nature of these findings, noting that this is the first Phase 3 trial in a dry eye chamber to achieve a positive result using a symptom as the primary endpoint. Dr. Brady expressed optimism about reproxalap's rapid clinical effect in reducing the discomfort associated with dry eye disease.

The study involved administering the placebo to patients before and during their exposure to a dry eye chamber, following the FDA's guidelines for such trials. Patients who met the qualification criteria were then randomly assigned to receive either reproxalap or the placebo before a second exposure to the dry eye chamber. Out of the 132 participants, 66 received reproxalap and 66 received the placebo. The primary endpoint focused on measuring ocular discomfort between 80 to 100 minutes of chamber exposure.

This trial was designed to fulfill the FDA's requirement for a New Drug Application (NDA) resubmission, which necessitated an additional well-controlled study to confirm the drug's positive effects on treating ocular symptoms of dry eye. The study protocol and statistical plan received feedback and approval from the FDA through its Special Protocol Assessment process.

Reproxalap stands out as the first investigational drug for dry eye disease with data supporting both acute and chronic activity in symptom reduction. It is also the first to show potential for chronic administration with acute efficacy in reducing ocular redness. Aldeyra plans to resubmit the NDA in 2024, with an anticipated six-month review period based on FDA guidelines.

Safety data from the trial indicated no significant safety concerns, with reproxalap being well-tolerated by patients. The most common side effect reported was mild and transient discomfort at the instillation site, with no treatment-related discontinuations. To date, reproxalap has been tested in over 2,500 patients.

Aldeyra Therapeutics is committed to the development of innovative therapies for immune-mediated and metabolic diseases, focusing on modulating protein systems rather than targeting single proteins. Their product pipeline includes several Reactive Aldehyde Species (RASP) modulators and other compounds aimed at treating a variety of systemic and retinal conditions. Reproxalap, specifically, is being developed for dry eye disease and allergic conjunctivitis, targeting RASP which are elevated in inflammatory diseases.

Overall, the positive outcome of this Phase 3 trial marks a significant step toward providing a new therapeutic option for patients suffering from dry eye disease and underscores Aldeyra's ongoing efforts to address unmet medical needs in the field of ophthalmology.