Aldeyra Therapeutics receives Special Protocol Assessment Agreement Letter from FDA for ADX-2191

Aldeyra Therapeutics announced it has received a Special Protocol Assessment Agreement Letter from the US Food and Drug Administration (FDA) for ADX-2191 (methotrexate injection, USP).

ADX-2191 is an investigational drug candidate from Aldeyra for the treatment of primary vitreoretinal lymphoma (PVRL), a rare and potentially fatal cancer with no current FDA-approved therapy. It is a sterile, non-compounded intravitreal formulation of methotrexate. ADX-2191 has received FDA Orphan Drug Designation for the treatment of primary vitreoretinal lymphoma and retinitis pigmentosa.

Aldeyra held a New Drug Application (NDA) meeting with the FDA in December 2022 and submitted a literature-based NDA of ADX-2191 for the treatment of PVRL, which was accepted for priority review in March 2023. The company received a complete response letter (CRL) from the FDA in June 2023 stating that the available literature was not sufficient to demonstrate efficacy and that adequate and well-controlled trials were required for approval. The FDA agreed that a single clinical trial in addition to literature references will be sufficient to support NDA resubmission, according to Aldeyra.

Todd C. Brady, MD, PhD, president and CEO of Aldeyra, commented in a press release from the company, saying, “Primary vitreoretinal lymphoma is treated today off-label with intravitreal injections of compounded methotrexate. ADX-2191, a novel, vitreous-compatible formulation of methotrexate that is specifically designed for intraocular injection, potentially allows for a reduced injection volume relative to compounding.”

The company noted that the clinical trial outlined in the Special Protocol Assessment will compare cancer cell clearance after 30 days of therapy in up to 20 patients following 1:1 randomization to receive either a single intraocular injection or 8 intraocular injections of ADX-2191. The company noted that the frequency of methotrexate injections has been linked to cancer cell clearance in patients with PVRL, and approximately 5 injections are required on average to achieve cancer cell clearance.

The clinical trial is expected to begin in the second half of 2025 and conclude in 2026.

Additionally, the company recently submitted its third new drug application for reproxalap for the treatment of dry eye disease. The company had received 2 CRLs from the FDA in April 2025 and November 2023 for past submissions.

References:

1. Aldeyra Therapeutics Receives Special Protocol Assessment Agreement Letter from the U.S. Food and Drug Administration for ADX-2191 for the Treatment of Primary Vitreoretinal Lymphoma. Published June 26, 2025. Accessed June 26, 2025. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-receives-special-protocol-assessment