FDA Accepts for Priority Review Drug for Rare Retinal Cancer

The FDA has accepted for priority review Aldeyra Therapeutic’s new drug application (NDA) for ADX-2191 (methotrexate) to treat patients with primary vitreoretinal lymphoma. The FDA assigned a Prescription Drug User Fee Act (PDUFA) date of June 21, 2023.

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.

ADX-2191 (methotrexate) 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, viscosity, density, tonicity, pH, concentration, and volume of administration.

Todd C. Brady, M.D., Ph.D.

“Compounding methotrexate for intravitreal injection, the current standard of care for primary vitreoretinal lymphoma, poses several challenges for physicians and patients, including risk of infection and increased injection volume, potentially leading to ocular hypertension and corneal inflammation,” Todd C. Brady, M.D., Ph.D., Aldeyra’s president and chief executive officer, said in a press release in December 2022 when the company submitted its NDA. “ADX-2191 is a novel formulation of methotrexate that is designed to be vitreous-compatible and has the potential to be the first marketed drug for patients suffering from primary vitreoretinal lymphoma.”

The NDA submission is supported by a combination of published literature on the safety and efficacy of methotrexate for the treatment of primary vitreoretinal lymphoma and safety data from the completed phase 3 GUARD Trial of ADX-2191 in patients with proliferative vitreoretinopathy. During the phase 3 GUARD Trial, no safety signals were observed, and ADX-2191 was well tolerated; there were no observed treatment-emergent serious adverse events. The most common adverse event associated with ADX‑2191 treatment was punctate keratitis, a frequently observed side effect of intravitreal methotrexate, that was most commonly mild in severity.