• TRANQUILITY Primary Endpoint of Ocular Redness Not Met, but Statistical Significance Achieved for Secondary Endpoint of Schirmer Test (p=0.0001), an Approvable Sign of Dry Eye Disease
  • Primary Endpoint of TRANQUILITY-2 Trial Modified to be Met if Either Ocular Redness or Schirmer Test Achieved; Target Enrollment Increased from 300 to up to 400 Patients; Top-Line Results Expected Mid-2022
  • Dry Eye Disease NDA Submission Expected Mid-2022, Pending Safety Trial Enrollment and Outcome of TRANQUILITY-2

LEXINGTON, MA, USA I December 20, 2021 I Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra or the Company), a biotechnology company developing novel immune-modulating therapies to treat ocular and systemic diseases, today announced top-line results from the Phase 3 TRANQUILITY Trial of 0.25% reproxalap ophthalmic solution (reproxalap), an investigational product candidate for the treatment of dry eye disease.

Although the primary endpoint of ocular redness was not met in TRANQUILITY, statistical significance (p=0.0001) was achieved for the dry eye disease sign of Schirmer test, a secondary endpoint. Statistical significance (p<0.0001) was also achieved for the post-hoc assessment of Schirmer test responders of ≥10 mm. The Schirmer test has been accepted by the U.S. Food and Drug Administration (FDA) as part of the basis of approval of other dry eye disease products. The primary endpoint of the upcoming Phase 3 TRANQUILITY-2 Trial has been modified such that the endpoint will have been met if either Schirmer test or ocular redness demonstrates stastisical significance. In addition, target enrollment in TRANQUILITY-2 has been increased from 300 to up to 400 patients. Top-line results from TRANQUILITY-2 are expected mid-2022.

“Following the achievement of statistical significance in ocular redness in our recent Phase 2 clinical trial, the achievement of statistical significance of Schirmer test in TRANQUILITY may provide an additional option to satisfy the remaining objective sign requirement for dry eye disease NDA submission,” stated Todd C. Brady, M.D., Ph.D., President and Chief Executive Officer of Aldeyra. “Subject to agreement with the FDA, we believe that the TRANQUILITY results allow for the possibility that, pending the outcome of TRANQUILITY-2, the NDA submission for reproxalap could represent the first time a dry eye disease drug will have qualified for the demonstration of activity for two objective signs.”

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 demonstrate efficacy in an objective sign in at least two clinical trials and efficacy in a subjective symptom in at least two clinical trials. To satisfy the symptom efficacy requirements, Aldeyra intends to submit two previously completed 12-week adequate and well-controlled symptom trials that pre-specified patient-reported ocular dryness score as a primary endpoint, the Phase 3 RENEW-Part 1 Trial and the Formulation Phase 2 clinical trial. Aldeyra’s recently completed Phase 2 clinical trial achieved the primary endpoint of ocular redness, an approvable sign of dry eye disease. Pending discussion with the FDA and the results of TRANQUILITY-2, Aldeyra may submit two pivotal trials for either ocular redness (Phase 2 and TRANQUILITY-2) or Schirmer test (TRANQUILITY and TRANQUILITY-2), or two trials for both signs (Phase 2, TRANQUILITY, and TRANQUILITY-2) if ocular redness and Schirmer test are achieved in TRANQUILITY-2. Phase 2 and Phase 3 clinical trials can be submitted as pivotal, provided that the trials are adequate and well-controlled.

Pending enrollment of the ongoing 12-month safety trial in dry eye disease patients and the outcome of TRANQUILITY-2, the dry eye disease NDA (New Drug Application) submission is expected to occur mid-2022. NDA submission for allergic conjunctivitis, another proposed indication, is expected to occur after the dry eye disease submission, and following completion of an additional allergen chamber trial requested by the FDA. Primary and key secondary endpoints in allergic conjunctivitis were previously achieved in the Phase 3 ALLEVIATE conjunctival allergen challenge trial and the Phase 3 INVIGORATE allergen chamber trial.

“Notwithstanding the inherent variability of dry eye disease clinical trials, our investigational product candidate 0.25% reproxalap has now demonstrated activity in four late-stage clinical trials with the intended commercial dosing regimen,” Dr. Brady stated. “We continue to advance reproxalap toward NDA submission as we focus on the completion of TRANQUILITY-2 and enrollment in the 12-month safety trial.”

No safety signals were observed in TRANQUILITY, and reproxalap was well tolerated; there were no treatment-related discontinuations or moderate or serious adverse events. Reproxalap has now been tested in over 1,500 patients. The most common reported adverse event is mild and transient instillation site discomfort.

About Reproxalap

Reproxalap, an investigational new drug, is a novel small-molecule immune-modulating covalent inhibitor of RASP (reactive aldehyde species), which are elevated in ocular and systemic inflammatory disease. Reproxalap’s mechanism of action has been validated with the demonstration of statistically significant and clinically relevant activity in multiple physiologically distinct late-phase clinical indications. Reproxalap is currently in Phase 3 clinical development as a 0.25% ophthalmic solution for the treatment of dry eye disease and allergic conjunctivitis, two ocular inflammatory diseases that often occur together.

About Dry Eye Disease

Dry eye disease is a common inflammatory disease estimated to affect 34 million or more adults in the United States.1 The disease is characterized by insufficient moisture and lubrication in the anterior surface of the eye, leading to dryness, inflammation, pain, discomfort, irritation, diminished quality of life, and in severe cases, permanent vision impairment. Among many physicians and patients, existing therapy for dry eye disease is generally regarded as inadequate and often requires weeks or months to demonstrate activity. In patients with dry eye disease, pro-inflammatory RASP may contribute to ocular inflammation and changes in tear lipid composition.2 By diminishing RASP levels, Aldeyra’s lead RASP inhibitor reproxalap represents a novel and differentiated approach for the treatment of the symptoms and signs of dry eye disease.

About Aldeyra Therapeutics, Inc.

Aldeyra Therapeutics, Inc. is a biotechnology company developing novel immune-modulating therapies to treat ocular and systemic diseases. Two of the Company’s lead product candidates, reproxalap and ADX-629, target RASP, which are pre-cytokine, systems-based mediators of inflammation. Reproxalap is being evaluated in Phase 3 clinical trials in patients with dry eye disease and allergic conjunctivitis. The Company’s clinical pipeline also includes ADX-2191 (methotrexate for intravitreal injection), a drug candidate in Phase 3 testing for the prevention of proliferative vitreoretinopathy. For more information, visit https://www.aldeyra.com/ and follow us on LinkedIn, Facebook, and Twitter.

1 Paulsen AJ, Cruickshanks KJ, Fischer ME, Huang GH, Klein BE, Klein R, Dalton DS. Dry eye in the beaver dam offspring study: prevalence, risk factors, and health-related quality of life. Am J Ophthalmol. 2014 Apr;157(4):799-806. doi: 10.1016/j.ajo.2013.12.023. Epub 2014 Jan 2. PMID: 24388838; PMCID: PMC3995164.

2 Choi W, Lian C, Ying L, Kim GE, You IC, Park SH, Yoon KC. Expression of Lipid Peroxidation Markers in the Tear Film and Ocular Surface of Patients with Non-Sjogren Syndrome: Potential Biomarkers for Dry Eye Disease. Curr Eye Res. 2016 Sep;41(9):1143-9. doi: 10.3109/02713683.2015.1098707. Epub 2016 Jan 5. PMID: 26731289.

SOURCE: Aldeyra Therapeutics