Aldeyra Therapeutics, Inc.Reproxalap Ophthalmic Solution

NDA 216442 COMPLETE RESPONSE

Aldeyra Therapeutics, Inc. Attention: David Noskowitz

Regulatory Affairs Consultant 131 Hartwell Ave., Suite 320 Lexington, MA 02421

Dear David Noskowitz:

Please refer to your new drug application (NDA)

for Reproxalap Ophthalmic Solution, ©® .

We acknowledge receipt of your amendment dated me) , which constituted a complete response to our oe , action letter. We acknowledge receipt of your major amendment dated oe , which extended the goal date by three months.

We have completed our review of this application, as amended, and have determined that we cannot approve this application in its present form. We have described our reasons for this action below and, where possible, our recommendations to address these issues.

There is a lack of substantial evidence consisting of adequate and well-controlled investigations, as defined in § 314.126, that the drug product will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in its proposed labeling. The application has 1 failed to demonstrate efficacy in adequate and well controlled studies in

The inconsistency of study results raises serious concerns about the reliability and meaningfulness of the positive findings. ADX-102-DED-012, ADX-102-DED-019, ADX- 102-DED-023, ADX-102-DED-030, ADX-102-DED-031 were failed trials. The totality of evidence from the completed clinical trials does not support the effectiveness of the product. We recommend that you explore the common reasons for treatment failure in the multiple failed trials. We also recommend that you attempt to identify populations or certain conditions in which the drug product may be effective.

PRESCRIBING INFORMATION

We reserve comment on the proposed labeling until the application is otherwise adequate. We encourage you to review the labeling review resources on the

Reference ID: 5763508

NDA 216442 Page 2

Prescription Drug Labeling Resources! and Pregnancy and Lactation Labeling Final Rule? websites, including regulations and related guidance documents and the Selected Requirements for Prescribing Information (SRPI) - a checklist of important format items from labeling regulations and guidances.

CARTON AND CONTAINER LABELING We reserve comment on the proposed labeling until the application is otherwise adequate.

PROPRIETARY NAME

Please refer to our correspondence dated, , which addresses the proposed proprietary name, I"). This name was found conditionally acceptable pending approval of the application in the current review cycle. Please resubmit the proposed proprietary name when you respond to all of the application deficiencies that have been identified in this letter.

(b) (4)

SAFETY UPDATE

When you respond to the above deficiencies, include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all nonclinical and clinical studies/trials of the product under consideration regardless of indication, dosage form, or dose level.

OTHER

Within one year after the date of this letter, you are required to resubmit or take other actions available under 21 CFR 314.110. If you do not take one of these actions, we may consider your lack of response a request to withdraw the application under

21 CFR 314.65. You may also request an extension of time in which to resubmit the application.

A resubmission must fully address the deficiency listed in this letter and should be clearly marked with "RESUBMISSION" in large font, bolded type at the beginning of the cover letter of the submission. The cover letter should clearly state that you consider this resubmission a complete response to the deficiency outlined in this letter. A partial response to this letter will not be processed as a resubmission and will not start a new review cycle.

You may request a meeting or teleconference with us to discuss what steps you need to take before the application may be approved. If you wish to have such a meeting, submit your meeting request as described in the draft guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products. The

1 https://www.fda.gov/drugs/laws-acts-and-rules/prescription-drug-labeling-resources 2 https://www.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-drugs- final-rule

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

Reference ID: 5763508

NDA 216442 Page 3

product may not be legally marketed until you have been notified in writing that this application is approved.

If you have any questions, please contact ye yyy ys.

Sincerely,

{See appended electronic signature page}

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

Reference ID: 5763508

Signature Page 1 of 1

This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record.

(b) (4)

03/16/2026 12:30:24 PM

Reference ID: 5763508