Aldeyra Therapeutics Secures FDA Agreement for ADX-2191 Clinical Trial Protocol

Aldeyra Therapeutics has received a Special Protocol Assessment (SPA) Agreement Letter from the US FDA for ADX-2191 (methotrexate injection, USP), an investigational therapy designed to treat primary vitreoretinal lymphoma (PVRL).

ADX‑2191: A Targeted Therapy for PVRL

ADX-2191 is being developed as a treatment for primary vitreoretinal lymphoma (PVRL), a rare and potentially fatal ocular cancer with no currently approved FDA therapies. It is a sterile, non-compounded intravitreal formulation of methotrexate specifically designed for intraocular use. The investigational drug has been granted FDA Orphan Drug Designation for both PVRL and retinitis pigmentosa.

Regulatory Pathway and FDA Feedback

A New Drug Application (NDA) meeting for ADX-2191 was held in December 2022, followed by the submission of a literature-based NDA for the treatment of primary vitreoretinal lymphoma (PVRL), which the FDA accepted for priority review in March 2023. However, in June 2023, the FDA issued a Complete Response Letter (CRL), stating that the submitted literature alone was insufficient to demonstrate efficacy. Subsequently, the FDA agreed that one well-controlled clinical trial, in addition to literature references, would be adequate to support the NDA resubmission.

SPA‑Backed Clinical Trial Design

Under the Special Protocol Assessment (SPA), Aldeyra will conduct a clinical trial comparing 30-day cancer cell clearance between two dosing regimens of ADX-2191: a single intraocular injection and eight intraocular injections, with patients randomized in a 1:1 ratio. The study aims to enroll up to 20 patients with primary vitreoretinal lymphoma (PVRL). The eight-injection regimen reflects the current average number of doses typically required to achieve cancer cell clearance.

CEO Commentary and Trial Timeline

“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,” stated Dr. Todd C. Brady, President and CEO of Aldeyra.

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