Aldeyra Plans to Resubmit New Drug Application for Reproxalap in Dry Eye Disease
About 4 months after receiving a complete response letter (CRL) from the FDA, Aldeyra Therapeutics announced a clinical development plan intended to enable resubmission of a new drug application (NDA) of topical ocular 0.25% reproxalap, an investigational RASP modulator, for the treatment of dry eye disease to the FDA. Following discussions with the FDA, Aldeyra intends to initiate a dry eye chamber clinical trial in the first half of 2024. Contingent on positive results from the planned clinical trial, NDA resubmission is expected in the second half of 2024. Based on FDA guidance, the planned review period for the potential NDA resubmission is expected to be 6 months.
“The planned dry eye chamber clinical trial, if successful, could represent the first pivotal demonstration of rapid improvement in the symptoms of dry eye disease, a potentially debilitating and increasingly pervasive condition that affects millions of patients worldwide,” Todd C. Brady, MD, PhD, President and Chief Executive Officer of Aldeyra, said in a company news release.
According to November's CRL from the FDA, no safety or manufacturing issues with reproxalap were identified. However, the FDA letter stated that the NDA did not demonstrate “efficacy in treating ocular symptoms associated with dry eyes” and that “at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye” needed to be conducted.
In the proposed dry eye chamber trial, patients will be administered vehicle before and during exposure to a dry eye chamber. Qualifying patients will subsequently be randomized to receive either reproxalap or vehicle before and during exposure to an additional dry eye chamber. Approximately 100 patients are expected to be enrolled to assess the primary endpoint of ocular discomfort. The design and statistical powering for the proposed trial are derived from four previously completed dry eye chamber clinical trials with reproxalap. Based on the data from the previous clinical trials, when analyzed with the planned trial design and statistical plan, ocular discomfort in the dry eye chamber following treatment with reproxalap was statistically lower than that of vehicle (P=0.0003). The planned clinical trial is expected to be more than 90% powered to detect a difference between treatment groups.
“Affecting hundreds of millions of people globally, dry eye disease is a multifactorial progressive disease that impacts quality of life,” Sumit Garg, MD, Professor of Ophthalmology at University of California Irvine, said in a company news release. “We are excited about the novel upstream mechanism of action of RASP modulation and the potential to provide rapid relief of signs and symptoms of dry eye.”
A clinical trial at a different dry eye chamber, in addition to a traditional 6-week field clinical trial, are expected to be conducted in parallel with the planned clinical trial as part of a comprehensive strategy designed to account for disease heterogeneity and potential differences in clinical sites and environment. Consistent with previously disclosed guidance and based on the current operating plan, cash and cash equivalents of $142.8 million as of December 31, 2023 are projected to be sufficient to fund operations beyond 2026.