Regulators indicated there was a lack of evidence of effectiveness and lack of clinical trials done to support the application.
The FDA has issued a complete response letter to Aldeyra Therapeutics on its new drug application (NDA) of ADX-2191 (methotrexate) to treat patients with primary vitreoretinal lymphoma (PVRL). The agency indicated there is a lack of evidence of effectiveness and lack of clinical trials done to support the application.
Primary vitreoretinal lymphoma is a rare, aggressive, and potentially fatal retinal cancer that is diagnosed in about 300 to 600 patients in the United States per year. The median survival for newly diagnosed patients is less than five years. No approved treatments are currently available, though injection of compounded methotrexate represents the current standard of care. But methotrexate is one of the cancer drugs that is currently in shortage.
ADX-2191 is a non-compounded formulation of methotrexate designed to be injected into the space in the back of the eye called the vitreous cavity. The ADX-2191 intravitreal formulation is preservative-free, and is optimized for excipient composition, concentration, and volume of administration.
ADX-2191 is under development to treat patients with proliferative vitreoretinopathy and retinitis pigmentosa, both of which are rare, sight-threatening retinal diseases. Top-line results from a phase 2 clinical trial in retinitis pigmentosa are expected soon.
Aldeyra did not conduct clinical trials specifically in patients with primary vitreoretinal lymphoma. Its NDA was based on a combination of published literature on the safety and efficacy of methotrexate in patients with primary vitreoretinal lymphoma, as well as safety data from the completed phase 3 GUARD Trial of ADX-2191 in patients with proliferative vitreoretinopathy, a complication of retinal detachment.
Aldeyra plans to discuss ADX-2191 for the treatment of PVRL with the FDA, including the potential to make it accessible these patients under an Expanded Access Program protocol.
“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,” Todd C. Brady, M.D., Ph.D., president and chief executive officer of Aldeyra.
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.