Aldeyra Therapeutics hits primary end point in 1 of 2 phase 3 trials for reproxalap

Aldeyra Therapeutics has achieved primary end point in one of its phase 3 trials of reproxalap for the treatment of dry eye disease, which the company will include in the resubmission of the new drug application (NDA) for the therapeutic candidate.¹ The dry eye chamber trial was statistically superior to the vehicle in terms of ocular discomfort and while the field trial missed statistical significance for the primary end point, it was consistent with previous field trials and will be submitted with the NDA submission as supportive data. The company intends to resubmit its NDA in mid-2025, pending a Type A meeting with the FDA.

​​“The dry eye chamber results announced today are representative of a number of clinical trials that highlight the potential rapid clinical effect of reproxalap on reducing ocular discomfort,” Todd C. Brady, MD, PhD, president and chief executive officer of Aldeyra, said in a press release. “With no notable baseline differences across treatment arms and highly statistically significant results in favor of reproxalap over vehicle, Aldeyra believes the data potentially address the FDA feedback in the Complete Response Letter received last month and we look forward to meeting with the FDA shortly.”

About the dry eye chamber trial

The phase 3 trial of 0.25% reproxalap was randomized, double masked, and vehicle controlled. In the chamber trial, reproxalap achieved statistical significance for the prespecified end point of ocular discomfort (n = 58) compared with the vehicle (n = 58). The measure was an ocular discomfort symptom score (0-100) from 80 to 100 minutes following chamber entry (LS mean difference [95% CI] -6.5 [-10.5, -2.5]; P = 0.002).

No safety signals or treatment-related discontinuations were reported in either of the recently completed clinical trials. Investigators observed reproxalap to be well tolerated. The most commonly reported adverse event was mild and transient instillation site discomfort, which is consistent with prior clinical trials.

The FDA accepts chamber trial results per its draft guidance for dry eye drug development, but they are rare for dry eye clinical trials. Also called a challenge-model trial, this trial design uses a controlled chamber to regulate temperature, air flow, humidity, and other environmental factors.² All other dry eye disease therapeutics on the market today have used a more traditional environmental exposure study, marking Aldeyra’s trials as particularly unique.

Because this data contains no notable differences in baseline scores across treatment arms, Aldeyra hopes it will address the concerns listed by the FDA in the Complete Response Letter it received in April 2025 following the most recent NDA submission in November 2024. At the time, the FDA had found no manufacturing or safety issues with reproxalap, but stated that the submission “failed to demonstrate efficacy in adequate and well controlled studies in treating ocular symptoms associated with dry eyes” and that “at least one additional adequate and well controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye” should be conducted. Additionally, the FDA expressed concerns that the data from the previous chamber trial may have affected interpretation of the results.³

“Pending positive results from the ongoing clinical trials and discussions with the FDA, we look forward to a potential NDA resubmission mid-year 2025,” Brady said in a press release at the time of the CRL in April. “Reproxalap remains the only late-stage topical ocular therapy suitable for chronic administration to have potentially demonstrated acute reduction in ocular redness, as well as reduction in ocular discomfort, highlighting rapid and broad activity for both the signs and symptoms of dry eye disease.”

References

1. Aldeyra Therapeutics achieves primary endpoint in phase 3 dry eye disease chamber trial of Reproxalap and plans NDA resubmission. Aldeyra Therapeutics. Press release. May 5, 2025. Accessed May 6, 2025. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-achieves-primary-endpoint-phase-3-dry-eye-0

2. Harp MD. FDA issues complete response letter to Aldeyra Therapeutics for resubmitted new drug application of reproxalap. Optometry Times. April 3, 2025. Accessed May 6, 2025. https://www.optometrytimes.com/view/fda-issues-complete-response-letter-to-aldeyra-therapeutics-for-resubmitted-new-drug-application-of-reproxalap

3. Dry eye: developing drugs for treatment - guidance for industry. FDA. December 14, 2020. Accessed May 6, 2025. https://www.fda.gov/media/144594/download