FDA Finds 'Substantive' Issues in Aldeyra’s NDA for Reproxalap for Dry Eye Disease

Aldeyra Therapeutics was dealt a major setback this week as the FDA identified "substantive review issues" in the company’s new drug application for dry-eye disease treatment candidate reproxalap.

In a US securities filing on Monday, Aldeyra cited minutes from a late-cycle review meeting in which the FDA is quoted as saying "[i]t does not appear that you have data to support the clinical relevance of the ocular signs to support your dry-eye indication."

In subsequent communications between Aldeyra and the FDA, Aldeyra said it submitted responses to the FDA that Aldeyra believes to be sufficient to mitigate the identified issues, but the FDA “has not directly opined on the sufficiency of the information submitted, has no legal obligation to review the information submitted by Aldeyra, and has indicated that Aldeyra needs to conduct an additional clinical trial to satisfy efficacy requirements,” according to the securities filing.

Aldeyra stated in the SEC document that the company’s ability to generate revenue depends on FDA approval and successful commercialization of reproxalap. “If Aldeyra is unable to successfully obtain FDA approval, or FDA approval is delayed or limited, Aldeyra’s ability to generate revenue will be significantly delayed,” the company stated.

Now facing a potential rejection or delay, the FDA feedback caused Aldeyra’s shares to drop about 67% at the close of trading Monday. The correspondence comes just over a month before the PDUFA target action date of November 23.

Reproxalap is a first-in-class small-molecule modulator of RASP (reactive aldehyde species), which are elevated in ocular and systemic inflammatory disease.

In February, the FDA accepted Aldeyra’s NDA for topical ocular reproxalap. The NDA was supported by safety and efficacy results from five clinical trials encompassing data for ocular dryness symptom score, ocular redness, Schirmer test, and Schirmer test ≥10 mm responder analysis. The NDA included activity ranging from within minutes of drug administration to up to 12 weeks of treatment, crossover and parallel-group clinical trial designs, and assessment in dry eye chamber challenge and natural environment settings. Reproxalap has been studied in more than 2,300 patients with no observed clinically significant safety concerns; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials, according to Aldeyra.

Aldeyra is also evaluating reproxalap in phase 3 trials for allergic conjunctivitis.