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Aldeyra Therapeutics Resubmits Reproxalap NDA in Dry Eye Disease
The company believes results from a recent phase 3 chamber trial fulfill the FDA’s requests in the Complete Response Letter received in April of 2025.
On June 17, 2025, Aldeyra Therapeutics announced the resubmission of a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for reproxalap, an investigational new drug candidate for the treatment of signs and symptoms of dry eye disease (DED).1
“Consistent with a number of clinical trials that suggest the potential of reproxalap to rapidly improve the symptoms of dry eye disease, we believe the clinical trial results included in the resubmission announced today are robust,” said Todd C. Brady, MD, PhD, president and chief executive officer of Aldeyra Therapeutics. “Based on the lack of notable baseline differences across treatment arms and the highly statistically significant achievement of the prespecified primary endpoint in favor of reproxalap over vehicle, in conjunction with recent FDA discussions, we believe that previous concerns raised by the FDA have been addressed.”1
Reproxalap is a first-in-class small-molecule modulator of reactive aldehyde species (RASP), which are elevated in ocular and systemic inflammatory diseases. The mechanism of action has been supported by demonstrations of statistically significant and clinically relevant activity in multiple physiologically distinct late-phase clinical indications.1
Reproxalap has been studied in >2900 patients without observed safety concerns. Mild and transient instillation site irritation is the most reported adverse event. Aldeyra is also currently testing reproxalap for the treatment of allergic conjunctivitis, another of the 2 largest markets in ophthalmology.1
On April 3, 2025, Aldeyra received a Complete Response Letter (CRL) from the FDA, which indicated possible methodological issues in a previous dry eye chamber trial, including baseline variance across treatment arms. The FDA implied these may have affected the interpretation of the results and requested an additional symptom trial before resubmission.2
On May 5, 2025, Aldeyra announced that their phase 3 trial of reproxalap had achieved its primary endpoint of statistical superiority over vehicle on ocular discomfort system score from 80-100 minutes after chamber entry (LS mean difference [95% CI] -6.5 [-10.5, -2.5], P = .002). A phase 3, randomized, double-masked, vehicle-controlled chamber trial testing 0.25% reproxalap ophthalmic solution, this trial notably included no significant differences in baseline scores across treatment arms.3
Aldeyra additionally undertook a field trial, which did not achieve statistical significance despite being numerically supportive of reproxalap and consistent with previous field trials. This will be submitted along with the NDA resubmission as supportive.3
According to Aldeyra, reproxalap is the first investigational drug with pivotal data supportive of acute and chronic activity in reducing symptoms of DED, and the first investigational drug for chronic administration with pivotal data supporting acute activity in reducing exacerbation of ocular redness.3
“The dry eye chamber results…are representative of a number of clinical trials that highlight the potential rapid clinical effect of reproxalap on reducing ocular discomfort,” Brady said. “With no notable baseline differences across treatment arms and highly statistically significant results in favor of reproxalap over vehicle, Aldeyra believes the data potentially addresses the FDA feedback in the Complete Response Letter…and we look forward to meeting with the FDA shortly.”3
References
Aldeyra Therapeutics Resubmits Reproxalap New Drug Application for the Treatment of Dry Eye Disease. Aldeyra Therapeutics, Inc. June 17, 2025. Accessed June 17, 2025. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-resubmits-reproxalap-new-drug-application-0
Livingston R. FDA Issues Complete Response Letter to Reproxalap for Dry Eye Disease. HCPLive. April 3, 2025. Accessed June 17, 2025. https://www.hcplive.com/view/fda-issues-complete-response-letter-to-reproxalap-for-dry-eye-disease
Aldeyra Therapeutics, Inc. Aldeyra Therapeutics Achieves Primary Endpoint in Phase 3 Dry Eye Disease Chamber Trial of Reproxalap and Plans NDA Resubmission. May 5, 2025. Accessed June 17, 2025. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-achieves-primary-endpoint-phase-3-dry-eye-0
