Reproxalap Receives Complete Response Letter From FDA for Use in Dry Eye Disease

Aldeyra Therapeutics has announced it received a complete response letter (CRL) from the FDA for its investigational topical drug reproxalap at a 0.25% dose for use in dry eye disease due to concerns around the data that could have affected the results.¹ This CRL comes after Aldeyra Therapeutics resubmitted their new drug application in October of 2024 following a previous CRL.²

Reproxalap is a reactive aldehyde species modulator that seeks to treat ocular discomfort in patients with dry eye disease. The treatment had previously been evaluated by the FDA in 2023 before the application was denied for lack of efficacy in dry eye disease. This new application comes after a phase 3 trial was conducted to attempt to confirm the treatment's efficacy.

The phase 3 dry eye chamber clinical trial enrolled 132 patients in June 2024 to conduct a 6-week trial of 0.25% reproxalap with the aim of comparing a control substance with reproxalap in chronic and acute improvements in symptoms and ocular redness.³ This clinical trial was the first to assess clinical data scutely in a dry eye chamber and the first to include reduction in ocular redness for a drug administered chronically.

Reproxalap met its primary end point of the phase 3 trial, with researchers finding that it was statistically superior to the vehicle for relieving ocular discomfort.⁴ Participants were administered the vehicle before and during exposure to a dry eye chamber prior to being randomized to receive either the vehicle or reproxalap before and during another dry eye chamber. Ocular discomfort from 80 to 100 minutes in the chamber acted as the primary end point.

Reproxalap was found to be safe and well tolerated,⁴ with the most common adverse event being mild and transient instillation site discomfort. None of the participants discontinued treatment.

These results were submitted along with 2 previously conducted trials around the efficacy of reproxalap in ocular redness and 2 trials on disease symptom field that were included in the first new drug application. However, the FDA stated that the application did not demonstrate efficacy in treating symptoms associated with dry eye and future studies are needed to gather these data. There are 3 ongoing trials aimed at assessing the efficacy of reproxalap that will be discussed in an upcoming meeting to determine next steps in the ongoing trials.

Aldeyra intends to resubmit their new drug application later this year pending positive results of their ongoing clinical trials.

“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," said Todd C. Brady, MD, PhD, CEO and president of Aldeyra Therapeutics.¹

References

1. Aldeyra Therapeutics receives complete response letter from the U.S. Food and Drug Administration for hte reproxalap new drug application for the treatment of signs and symptoms of dry eye disease. News release. Aldeyra; April 3, 2025. Accessed April 3, 2025. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-receives-complete-response-letter-us-food-0
2. Maharjan EK, Harp MD. FDA accepts NDA from Aldeyra Therapeutics for preproxalap for dry eye. Ophthalmology Times^®. November 19, 2024. Accessed April 1, 2025. https://www.ophthalmologytimes.com/view/fda-accepts-nda-from-aldeyra-therapeutics-for-reproxalap-for-dry-eye
3. Aldeyra Therapeutics completes enrollment in phase 3 clinical trial of reproxalap in dry eye disease. News release. Aldeyra; June 13, 2024. Accessed April 1, 2025. https://www.businesswire.com/news/home/20240613335679/en/Aldeyra-Therapeutics-Completes-Enrollment-in-Phase-3-Clinical-Trial-of-Reproxalap-in-Dry-Eye-Disease
4. Aldeyra Therapeutics achieves primary endpoint in phase 3 dry eye disease clinical trial of reproxalap. News release. Aldeyra; August 8, 2024. Accessed April 1, 2025. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-achieves-primary-endpoint-phase-3-dry-eye