Aldeyra Resubmits New Drug Application for Reproxalap for Dry Eye Disease

Credit: US Food and Drug Administration

Aldeyra Therapeutics has resubmitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for their investigational new drug candidate, topical ocular reproxalap, for the treatment of signs and symptoms of dry eye disease (DED).¹

Announced on October 3, 2024, the resubmitted NDA for reproxalap included positive results from a recently finished Phase 3 DED symptom trial requested by the FDA, following a review of the previously submitted NDA. In November 2023, Aldeyra received a Complete Response Letter (CRL) after failing to demonstrate “efficacy in treating ocular symptoms associated with dry eyes,” according to the FDA.²

The resubmitted NDA also involved a draft label reflecting acute activity in reducing dry eye symptoms in a dry eye chamber trial, chronic activity in reducing dry eye symptoms in a field trial, and acute activity in reducing ocular redness in two dry eye chamber trials.¹

“If approved, reproxalap would have the potential to be the first DED therapy for chronic use with pivotal data demonstrating acute activity in reducing dry eye symptoms and ocular redness, two characteristics of DED of primary importance to patients,” said Todd C. Brady, MD, PhD, president and chief executive officer of Aldeyra.¹

Reproxalap is a first-in-class small-molecule modulator of reactive aldehyde species (RASP), a pre-cytokine mediator of inflammation typically elevated in ocular and systemic inflammatory diseases.³ In the Phase 3 randomized, double-masked, vehicle-controlled dry eye chamber trial, reproxalap was statistically superior to vehicle for the prespecified primary endpoint of ocular discomfort (P = .004), an FDA-approved symptom of DED.⁴

Patients in the trial were administered vehicle before and during exposure to a dry eye chamber, which Aldeyra believes remained consistent with the FDA’s DED draft guidance. Those who met the criteria were then randomized to receive reproxalap or vehicle before and during exposure to an additional dry eye chamber. Among the 132 randomized patients, 66 received reproxalap and 66 received the vehicle.

Ocular discomfort, an FDA-accepted symptom of DED, was measured from 80 to 100 minutes in the chamber. Aldeyra designed the dry eye chamber clinical trial to meet the FDA’s NDA resubmission requirement of “at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye.”

According to Aldeyra, these results were the first positive Phase 3 clinical trial data in a dry eye chamber with a symptom as the primary endpoint.¹ The company indicated these results support the potential rapid clinical effect of reproxalap in reducing DED-associated ocular discomfort.

Aldeyra expects the resubmission NDA review period to be completed within 6 months, based on The Prescription Drug User Fee Act (PDUFA) target guidelines for NDA resubmissions.¹

References

1. _{Aldeyra Therapeutics resubmits Reproxalap New Drug Application for the treatment of dry eye disease. Aldeyra Therapeutics, Inc. October 3, 2024. Accessed October 3, 2024. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-resubmits-reproxalap-new-drug-application.}
2. _{Aldeyra Therapeutics receives complete response letter from the U.S. Food and Drug Administration for the REPROXALAP New Drug Application for the treatment of dry eye disease. Aldeyra Therapeutics, Inc. November 27, 2023. Accessed October 3, 2024. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-receives-complete-response-letter-us-food.}
3. _{Clark D, Cavanagh B, Shields AL, Karpecki P, Sheppard J, Brady TC. Clinically Relevant Activity of the Novel RASP Inhibitor Reproxalap in Allergic Conjunctivitis: The Phase 3 ALLEVIATE Trial. Am J Ophthalmol. 2021;230:60-67. doi:10.1016/j.ajo.2021.04.023}
4. _{Aldeyra Therapeutics achieves primary endpoint in phase 3 dry eye disease clinical trial of Reproxalap. Aldeyra Therapeutics, Inc. August 8, 2024. Accessed October 3, 2024. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-achieves-primary-endpoint-phase-3-dry-eye.}