LEXINGTON, Mass.--(BUSINESS WIRE)--Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra) today reported that a post-hoc analysis using computer automated grading of digital photography from the completed Phase 3 TRANQUILITY dry eye chamber trial demonstrated statistical significance (p=0.020) in favor of reproxalap over vehicle for the primary endpoint of reduction of ocular redness. As previously announced, the Phase 3 TRANQUILITY trial failed to meet the primary endpoint of ocular redness as assessed by independent central reviewers.
When applied to Aldeyra’s Phase 2 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 3 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,1 with the FDA prior to NDA submission.
The computer automated grading of redness in the completed Phase 3 TRANQUILITY and Phase 2 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 3 TRANQUILITY and Phase 2 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 3 RENEW-Part 1 and Formulation Phase 2 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 3 TRANQUILITY and Phase 2 dry eye chamber trials. If the primary endpoint of Schirmer test is achieved in the Phase 3 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.
Aldeyra develops innovative therapies designed to treat immune-mediated diseases. Our approach is to discover pharmaceuticals that modulate immunological systems, instead of directly inhibiting or activating single protein targets, with the goal of optimizing multiple pathways at once while minimizing toxicity. Two of our lead product candidates, reproxalap and ADX-629, target pre-cytokine, systems-based mediators of inflammation known as RASP (reactive aldehyde species). Reproxalap is in Phase 3 clinical trials in patients with dry eye disease and allergic conjunctivitis. ADX-629, an orally administered RASP modulator, is in Phase 2 clinical testing for the treatment of systemic immune-mediated diseases. Our pipeline also includes ADX-2191 (intravitreal methotrexate 0.8%), in development for the prevention of proliferative vitreoretinopathy and the treatment of retinitis pigmentosa and primary vitreoretinal lymphoma. For more information, visit https://www.aldeyra.com/ and follow us on LinkedIn, Facebook, and Twitter.
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In addition to the risks described above and in Aldeyra's other filings with the SEC, other unknown or unpredictable factors also could affect Aldeyra's results. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. The information in this release is provided only as of the date of this release, and Aldeyra undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law.
1 Rodriguez JD et al. Automated grading system for evaluation of ocular redness associated with dry eye. Clin Ophthalmol. 2013;7:1197-1204.