Did the FDA agree to the design of Aldeyra's 2024 dry eye chamber trial?

Aldeyra Therapeutics Form 8-K, filed August 8, 2024

In the Phase 3 clinical trial, patients were administered vehicle (the drug product without the active ingredient) before and during exposure to a dry eye chamber in a manner that Aldeyra believes is consistent with the FDA’s dry eye disease draft guidance 1 . Qualifying patients were subsequently randomized to receive either reproxalap or vehicle before and during exposure to an additional dry eye chamber. Of the 132 patients randomized, 66 patients received reproxalap and 66 patients received vehicle. The primary endpoint was ocular discomfort, an FDA-accepted symptom of dry eye disease, from 80 to 100 minutes in the chamber.

Aldeyra Therapeutics Form 8-K, filed August 8, 2024

The dry eye chamber clinical trial was designed to satisfy the FDA’s New Drug Application (NDA) resubmission requirement, identified in the previously received complete response letter, of “at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye.” Through the FDA Special Protocol Assessment process and additional comments, the FDA provided feedback on the clinical trial protocol and statistical plan.

FDA Complete Response Letter, April 2, 2025 · page 2

You used Visit 2 and Visit 4 DEC results as the dependent variable and performed linear contrasts to obtain treatment differences between Visit 4 and Visit 2 results. The Agency finds the Study 030 primary efficacy endpoint analysis problematic, and we do not find the study results to be robust.

FDA Complete Response Letter, April 2, 2025 · page 2

You should conduct at least one additional adequate and well controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye. In the conduct of this study, you should not make changes to the protocol or the statistical analysis plan after the first subject is enrolled in the study without expressed agreement by the FDA.

Aldeyra Therapeutics Form 10-K, filed February 27, 2026

On November 16, 2023, Aldeyra submitted to the FDA a Special Protocol Assessment (SPA) for a proposed Phase 3 clinical trial to assess ocular discomfort in a dry eye chamber, which is designed to simulate dry eye exacerbations or flares, potentially the most bothersome aspect of the disease for most dry eye patients. In response to the SPA, the FDA issued a SPA - No Agreement letter which provided feedback to Aldeyra on the proposed chamber trial. Based on the feedback, Aldeyra amended the design and protocol of the chamber trial and, per FDA SPA Guidance, Aldeyra and the FDA held a Type A meeting, during which we believe that the FDA concurred with the principal aspects of the trial design.

Aldeyra Therapeutics Form 10-K, filed February 27, 2026

Subsequent to the SPA Type A meeting, two chamber trials were initiated, in addition to one field trial, in which patients administered reproxalap or vehicle (placebo) over six weeks and reported ocular discomfort weekly.

Aldeyra Therapeutics Form 8-K, filed September 29, 2026

Trial Design Endpoint Reproxalap Improvement vs. Vehicle (%) 012 Field Symptoms 204% 012 Field Staining 21% 013 Field Symptoms 62% 019 Chamber Redness 0% 023 Chamber Schirmer Test 417% 023 Chamber Schirmer Response 113% 024 Chamber Redness 63% 024 Chamber Symptoms 11% 024 Chamber Schirmer Test 37% 027 Chamber Redness 34% 027 Chamber Schirmer Test 93% 030 Chamber Symptoms 66% 031 Field Symptoms 34% 032 Chamber Symptoms 102