FDA accepts NDA for priority review for ADX-2191 for treatment of rare retinal cancer

ADX-2191 is a sterile, non-compounded intravitreal formulation of methotrexate for the potential prevention or treatment of specific rare retinal diseases. (Image Credit: Adobe Stock/wladimir1804)

Aldeyra Therapeutics Inc. announced that the FDA accepted for Priority Review the New Drug Application (NDA) for ADX-2191 (methotrexate injection, USP) for the treatment of primary lymphoma.

Aldeyra had previously submitted the NDA to the FDA in December 2022.

Primary vitreoretinal lymphoma is a rare, aggressive, and potentially fatal retinal cancer that is diagnosed in approximately 300 to 600 patients in the United States per year, with a median survival for newly diagnosed patients of less than 5 years. There are currently no approved treatments available.

Todd C. Brady, MD, PhD, Aldeyra’s president and CEO, discussed the importance of this treatment for this rare cancer in a press release from the company.¹

“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,” Brady said in the statement. “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.”

According to a press release from the company,² ADX-2191 is a sterile, non-compounded intravitreal formulation of methotrexate for the potential prevention or treatment of specific rare retinal diseases, including primary vitreoretinal lymphoma, proliferative vitreoretinopathy, and retinitis pigmentosa. The release also states the intravitreal formulation is preservative-free and designed to be vitreous-compatible, and is optimized for excipient composition, viscosity, density, tonicity, pH, concentration, and volume of administration. 

Brady further elaborated on the importance of this treatment for this rare cancer in the release.

“The FDA’s decision to grant Priority Review with a PDUFA date four months from NDA acceptance underscores the significant need for an FDA-approved treatment of primary vitreoretinal lymphoma, a rare but potentially fatal cancer,” said Brady. “We are working closely with the FDA during the review process to bring ADX2191 to patients as quickly as possible, and plan to launch ADX-2191 in the United States in the second half of this year, pending approval by the FDA.”

The company stated the NDA submission is supported by “a combination of more than 3 decades of published literature on the safety and efficacy of methotrexate, the active ingredient of ADX2191, for the treatment of primary vitreoretinal lymphoma.” According to the company, the recently completed Phase 3 GUARD Trial showed that ADX-2191 was well tolerated with no observed treatment-emergent serious adverse events. The most common adverse event associated with ADX2191 treatment was punctate keratitis, a frequently observed side effect of intravitreal methotrexate, that was most commonly mild in severity.

According to the company’s website, ADX-2191 is also being researched for the treatment of proliferative vitreoretinopathy (PVR), a rare inflammatory disorder of the retina that leads to severe retinal scarring and blindness and is the leading cause of failure of retinal reattachment surgery. It is also currently undergoing a Phase 2 trial for the treatment of retinitis pigmentosa.

The FDA assigned a Prescription Drug User Fee Act (PDUFA) date of June 21, 2023 and noted that no potential filing review issues have been identified.

References:

1. Aldeyra Therapeutics submits new drug application to the U.S. Food and Drug Administration for ADX2191 for the treatment of primary vitreoretinal lymphoma. Press release. Aldeyra Therapeutics; December 21, 2022. Accessed March 2, 2023. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-submits-new-drug-application-us-food-and-0

2. FDA Accepts for priority review ADX-2191 new drug application for the treatment of primary vitreoretinal lymphoma. Press release. Aldeyra Therapeutics; March2, 2023. Accessed March 2, 2023. https://ir.aldeyra.com/news-releases/news-release-details/fda-accepts-priority-review-adx-2191-new-drug-application