Post-hoc analysis using computer automated grading of phase III TRANQUILITY trial digital photography demonstrated statistical significance in favour of reproxalap over vehicle for primary endpoint of ocular redness.

As previously announced, the Phase III TRANQUILITY trial failed to meet the primary endpoint of ocular redness as assessed by independent central reviewers. When applied to Aldeyra’s Phase II dry eye chamber trial, which was completed in late 2021, the computer automated grading assessment (p=0.003) confirmed the previously announced achievement of the primary endpoint of ocular redness (p=0.016), which, similar to the Phase III TRANQUILITY trial, was originally assessed by independent central reviewers. Aldeyra intends to discuss the results of the post-hoc analyses, as well as the algorithm used for the computer automated assessment of ocular redness, with the FDA prior to NDA submission.

The computer automated grading of redness in the completed Phase III TRANQUILITY and Phase II clinical trials of reproxalap is based on digital images captured by portable cameras fitted with eye cups to standardize distance, lighting, focus, hue, and contrast. The assessment consisted of automated selection of temporal conjunctiva from images of subjects focusing on nasal targets in the eye cup. Redness intensity was averaged across all pixels in the selected region, and combined with vessel geometry to generate a theoretical maximum score of 255. The average baseline score from the post-hoc analyses of the Phase III TRANQUILITY and Phase II clinical trials was approximately 18.

Per draft FDA guidance, to be considered for regulatory approval in the United States, a product candidate for the treatment of dry eye disease must, with certain exceptions, demonstrate efficacy in an objective sign in at least two clinical trials and efficacy in a subjective symptom in at least two clinical trials. Statistical significance versus vehicle is generally considered sufficient for demonstration of efficacy.

For satisfaction of symptom efficacy requirements, Aldeyra intends to submit two previously completed adequate and well-controlled 12-week symptom trials that pre-specified patient-reported ocular dryness score as a primary endpoint, the Phase III RENEW-Part 1 and Formulation Phase II clinical trials. Pending discussion with the FDA, for satisfaction of the sign efficacy requirements, Aldeyra intends to submit the ocular redness results from the Phase III TRANQUILITY and Phase II dry eye chamber trials. If the primary endpoint of Schirmer test is achieved in the Phase III TRANQUILITY-2 trial, and pending discussion with the FDA, Aldeyra intends to submit Schirmer test results from both TRANQUILITY trials as evidence for achievement of an additional objective sign of dry eye disease.

Top-line results from TRANQUILITY-2 are expected in the second quarter of 2022. Pending discussion with the FDA and enrollment of the ongoing 12-month safety trial in dry eye disease patients, NDA submission for dry eye disease is expected to occur mid-2022.