Aldeyra Therapeutics · Nasdaq: ALDX · Reproxalap ophthalmic solution

Aldeyra's 8-K of April 3, 2025 quotes the FDA's requirement for another study and mentions the baseline differences. It does not name Study 030 or Study 024, mention the analysis in which Study 030 is not statistically significant, or mention the letter's condition on protocol and analysis-plan changes.

On baselines the letter says “Ideally, baseline scores between groups should be similar” [FDA · Apr 2 · p. 2]; the 8-K says the FDA's concerns included “a difference in baseline scores across treatment arms” [8-K · Apr 3].

The letter says “The Agency finds the Study 030 primary efficacy endpoint analysis problematic” [FDA · Apr 2 · p. 2] and that, analyzed like Study 024, “the study does not achieve statistical significance” [FDA · Apr 2 · p. 2]. The 8-K does not name Study 030 or Study 024 and does not mention that analysis. [8-K · searched]

The 8-K quotes the letter's 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” [8-K · Apr 3] and says the company intends to “resubmit the NDA mid-year 2025” [8-K · Apr 3]. The letter's next sentence says the company “should not make changes to the protocol or the statistical analysis plan after the first subject is enrolled in the study without expressed agreement by the FDA” [FDA · Apr 2 · p. 2]. The 8-K does not mention that condition. [8-K · searched]

The 2025 letter asked for at least one more adequate and well-controlled study. The company says the 2026 letter did not recommend more trials; as the company quotes it, it cited inconsistent results and the totality of evidence.

The 2025 letter: “You should conduct at least one additional adequate and well controlled study” [FDA · Apr 2 · p. 2]. The company then reported a new chamber trial, and says its June 2025 resubmission “primarily consisted of results from the additional dry eye chamber trial” [8-K · Mar 17]; in December the FDA “requested submission of the clinical study report for the field trial” [8-K · Mar 17].

Of the 2026 letter, the 8-K says “The FDA did not recommend conducting additional trials or request submission of additional confirmatory evidence” [8-K · Mar 17], and quotes the letter: the “inconsistency of study results raises serious concerns about the reliability and meaningfulness of the positive findings” [8-K · Mar 17]. It also says “label drafts were provided by the FDA in December 2025 and again in March 2026” [8-K · Mar 17].

In September 2026 the company said it has “received three Complete Response Letters” [8-K · Sep 29] and has provided data from nine trials, “five of which achieved all multiplicity-controlled primary endpoints” [8-K · Sep 29]. Its table gives, for Study 030, “030 Symptoms ✓ Methodological issues Endpoint met, methodological sensitivity testing supportive of outcome” [8-K · Sep 29], noting that “FDA position is Aldeyra’s abbreviated interpretation of FDA review” [8-K · Sep 29].

The FDA's April 2025 letter found the Study 030 analysis problematic and asked for at least one more adequate and well-controlled study. Its March 2026 letter, as the company's 8-K quotes it, cited the inconsistency of study results and said the totality of evidence does not support effectiveness.

In the April 2025 letter, the items on page 2 concern baselines (“It is not clear that the models proposed by you adequately account for the difference in baseline” [FDA · Apr 2 · p. 2]), the FDA wrote: “The Agency finds the Study 030 primary efficacy endpoint analysis problematic, and we do not find the study results to be robust” [FDA · Apr 2 · p. 2]. When Study 030 is analyzed the way Study 024 was, “the study does not achieve statistical significance” [FDA · Apr 2 · p. 2].

It required: “You should conduct at least one additional adequate and well controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye” [FDA · Apr 2 · p. 2], adding that the company “should not make changes to the protocol or the statistical analysis plan after the first subject is enrolled in the study without expressed agreement by the FDA” [FDA · Apr 2 · p. 2].

For the March 2026 letter, the company's 8-K quotes it as saying the “inconsistency of study results raises serious concerns about the reliability and meaningfulness of the positive findings” [8-K · Mar 17] and that the “totality of evidence from the completed clinical trials does not support the effectiveness of the product” [8-K · Mar 17]. The 8-K says “The FDA recommended that the reasons for failure in certain trials be explored” [8-K · Mar 17]. Both letters say a resubmission must “fully address the deficiency listed in this letter” [FDA · Mar 16 · p. 2].

Page 1 of each published letter is a scanned image with no text layer, so this page does not check its wording; quotations of it here come from the company's 8-Ks. [not in record]

After Type A and Type D meetings, Aldeyra intends to submit a formal dispute resolution request appealing the March 2026 letter, with a meeting expected in the fourth quarter of 2026; it says the timing of a decision is uncertain.

On July 15, 2026 the company said it had received minutes of the June 10 Type A meeting and “requested a clarification of the Minutes from the FDA” [8-K · Jul 15]. Its 10-Q of Aug 6 says “we may decide to submit a formal dispute resolution request to the FDA” [10-Q · Aug 6].

On Sep 29, 2026 it announced an FDRR “designed to appeal the March 16, 2026 Complete Response Letter” [8-K · Sep 29], with “Submission of the FDRR and a meeting with the OND are expected in the fourth quarter of 2026” [8-K · Sep 29]. It says the decision's timing depends on factors “the occurrence and timing of which are uncertain” [8-K · Sep 29].

Not in this record: the FDA's meeting minutes, the 2023 letter, page 1 of the two published letters, and Aldeyra's filings after September 29, 2026. [not in record]