The New Drug Application (NDA) for ADX-2191 (methotrexate injection) has been submitted to the Food and Drug Administration (FDA) for the treatment of primary vitreoretinal lymphoma.

Primary vitreoretinal lymphoma is a rare retinal cancer characterized by blurred vision, painless loss of vision, floaters, red eye, and photophobia. ADX-2191 is a preservative-free, intravitreal formulation of methotrexate designed to be vitreous-compatible. 

The NDA is supported by safety data from the phase 3 GUARD trial ( Identifier: NCT04136366) which compared repeated intravitreal injections of ADX-2191 to standard of care for the prevention of proliferative vitreoretinopathy, along with published literature on the safety and efficacy of methotrexate for the treatment of primary vitreoretinal lymphoma.

Findings from the GUARD trial showed that ADX-2191 was well tolerated with no safety signals and treatment-emergent serious adverse events observed. The most common adverse event for ADX-2191 was punctate keratitis, which was mild in severity. 

The FDA previously granted Orphan Drug designation to ADX-2191 for this indication.

“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,” stated Todd C. Brady, MD, PhD, Aldeyra’s President and CEO. “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 Company is also investigating ADX-2191 for the prevention of proliferative vitreoretinopathy and for the treatment of retinitis pigmentosa. 


Aldeyra Therapeutics submits New Drug Application to the US Food and Drug Administration for ADX‑2191 for the treatment of primary vitreoretinal lymphoma. News release. Aldeyra Therapeutics. Accessed December 21, 2022.