Aldeyra Therapeutics Provides Regulatory Update on ADX-2191

(Nasdaq: ALDX) (Aldeyra), a biotechnology company devoted to discovering and developing innovative therapies designed to treat immune-mediated diseases, today announced receipt of a Complete Response Letter from the U.S. Food and Drug Administration (FDA) for the 505(b)(2) New Drug Application (NDA) of ADX-2191 (methotrexate for injection, USP), an investigational drug candidate, for the treatment of primary vitreoretinal lymphoma (PVRL). Although no safety or manufacturing issues with ADX-2191 were identified, the FDA stated that there was a “lack of substantial evidence of effectiveness” due to “a lack of adequate and well-controlled investigations” in the literature-based NDA submission. Based on prior discussions with the FDA, Aldeyra did not conduct any clinical trials of ADX-2191 in PVRL.

“While we appreciate the FDA’s position with respect to providing evidence from adequate and controlled trials, we do not currently believe that randomized clinical trials of ADX-2191 in PVRL, a rare and fatal cancer with no approved therapy, are feasible,” stated Todd C. Brady, M.D., Ph.D., President and Chief Executive Officer of Aldeyra Therapeutics. “Given the current shortage of methotrexate, the lack of approved therapy for PVRL, and the desire to avoid potential safety risks associated with ocular injection of compounded formulations, we look forward to discussing with the FDA the potential for making ADX-2191 available to PVRL patients under an Expanded Access Program.”

PVRL is a rare, high-grade, aggressive cancer, with a median survival of less than five years.¹ Methotrexate, the compounded intravitreal injection of which is the standard of care for the treatment of PVRL,² is currently in shortage, per the FDA Drug Shortages database. An Expanded Access Program allows for access to treatment options for serious diseases when other therapeutic options are not available. Aldeyra plans to discuss ADX-2191 for the treatment of PVRL with the FDA, including the potential to make ADX-2191 accessible to PVRL patients under an Expanded Access Program protocol.

ADX-2191 is also under development for the treatment of proliferative vitreoretinopathy and retinitis pigmentosa, both of which are rare, sight-threatening retinal diseases. Top-line results from a Phase 2 clinical trial of ADX-2191 in retinitis pigmentosa are expected to be announced in June of 2023. Additionally, Aldeyra plans to conduct a Type C meeting with the FDA in the second half of 2023 to discuss the completion of clinical development of ADX-2191 for the prevention of proliferative vitreoretinopathy.