FDA Denies Reproxalap NDA Resubmission

The U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Aldeyra Therapeutics, declining to approve the resubmitted New Drug Application (NDA) for reproxalap, the company’s investigational treatment for dry eye disease.

FDA Cites Efficacy Concerns Despite No Safety or Manufacturing Issues

According to the FDA, the NDA failed to demonstrate efficacy in “adequate and well-controlled studies” for treating ocular symptoms of dry eye disease. Although no safety or manufacturing concerns were raised, the agency concluded that at least one additional trial would be needed to demonstrate a positive effect.

The FDA also expressed concerns regarding data from previously submitted trials, noting potential methodological issues, including baseline score differences across treatment arms, which may have impacted interpretation of the results.

Background: Clinical Trials and Regulatory Timeline

To support its original NDA filed in November 2022, Aldeyra included:

• Two ocular redness trials conducted in dry eye chambers

• Two symptom-based field trials involving environmental exposure

Following a CRL in November 2023, which requested at least one more symptom trial, Aldeyra initiated three new trials as part of its revised strategy:

1. A dry eye chamber trial

2. A second chamber trial at a different site

3. A 6-week field trial

In August 2024, the company announced it had met the primary endpoint in the first of the new chamber trials. The NDA was subsequently resubmitted in October 2024.

Next Steps and Future Plans

Aldeyra anticipates a Type A meeting with the FDA within the next 30 days to discuss the CRL and the progress of its ongoing trials. The company expects to announce topline results from both the field and second chamber trials in Q2 2025.

Pending positive outcomes and further discussions with the FDA, Aldeyra plans to resubmit the NDA mid-year 2025. The standard review period for this potential resubmission is expected to be 6 months.

Financial Outlook

As of December 31, 2024, Aldeyra reported $101 million in cash, cash equivalents, and marketable securities. With most trial costs incurred in 2024, the projected expense for the ongoing clinical trials in 2025 is approximately $6 million.

Company Outlook on Reproxalap

“Pending positive results from the ongoing clinical trials and discussions with the FDA, we look forward to a potential NDA resubmission mid-year 2025,” said Todd C. Brady, MD, PhD, President and CEO of Aldeyra Therapeutics.
“Reproxalap remains the only late-stage topical ocular therapy suitable for chronic administration to have potentially demonstrated acute reduction in ocular redness and discomfort, supporting its broad and rapid activity across both signs and symptoms of dry eye disease.”