Aldeyra Therapeutics announces top-line results from the phase III TRANQUILITY trial of 0.25% reproxalap in 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 greater than 10 mm. the schirmer test has been accepted by the fda as part of the basis of approval of other dry eye disease products.

The primary endpoint of the upcoming Phase III TRANQUILITY-2 Trial has been modified such that the endpoint will have been met if either Schirmer test or ocular redness demonstrates statistical 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 II 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 III RENEW-Part 1 Trial and the Formulation Phase II clinical trial. Aldeyra’s recently completed Phase II 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 II and TRANQUILITY-2) or Schirmer test (TRANQUILITY and TRANQUILITY-2), or two trials for both signs (Phase II, TRANQUILITY, and TRANQUILITY-2) if ocular redness and Schirmer test are achieved in TRANQUILITY-2. Phase II and Phase III 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 III ALLEVIATE conjunctival allergen challenge trial and the Phase III 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.