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Aldeyra Therapeutics Inc., (NASDAQ: ALDX) reports the completion of enrollment in a Phase 2 study for methotrexate to treat Pro23His retinitis pigmentosa (RP)

Aldeyra Therapeutics, Inc. (NASDAQ: ALDX), a clinical stage company based in Lexington, Massachusetts, has reported the completion of the enrollment of a Phase 2 clinical trial of ADX-2191 (intravitreal methotrexate 0.8%), an investigational new drug product, for the treatment of retinitis pigmentosa (RP).  ADX-2191 is an intravitreal formulation of methotrexate, aimed to inhibit cellular replication and activation, and the company suggests that this formulation may induce a benefit to clear the misfolded rhodopsin protein, thereby potentially treating forms of RP characterized by a misfolded rhodopsin. In August 2021, ADX-2191 has been granted orphan drug designation by the U.S. Food and Drug Administration for the treatment of RP.


RP is a clinical group of rare genetic eye diseases characterized by retinal cell death and loss of vision and there are no approved treatments for RP.  Almost 300 genes have been identified that are involved in phototransduction, outer segment morphogenesis, cell trafficking and rhodopsin recycling pathways. Despite this considerable progress in identifying the primary, genetic “cause” of RP, the secondary “effect” likely descends on a final common pathway of slow apoptotic cell death of the rod photoreceptors, followed by the apoptotic cell death of the cone photoreceptors leading to complete loss of vision. While treatments for therapy have focused on considerable research on the primary causes of RP, therapeutic opportunities on inhibiting cell death may provide active apoptotic research.  Currently, these identified genes for retinal disease is likely to be a continuum of dystrophies with partially overlapping clinical and genetic findings and, in terms of the autosomal dominant Pro23His rhodopsin version, a particular group suggests that an estimated 82,000-110,000 individuals in the United States, and approximately 1 in 4,000 people worldwide, may be targeted for this current experimental treatment.


The open-label, single-centre Phase 2 clinical trial enrolled a total of eight retinitis pigmentosa patients receiving either monthly or twice-monthly intravitreal doses of ADX‑2191 for three months. The primary endpoint of the trial is adverse events and with secondary endpoints for visual acuity, retinal function, as assessed by foveal microperimetry, electroretinography, and dark adaptation and retinal morphology, as assessed by optical coherence tomography.  Commenting on the completion trial, Todd C. Brady, M.D., Ph.D., President and Chief Executive Officer of Aldeyra stated that “given the lack of FDA-approved therapies for retinitis pigmentosa, a sight-threatening group of diseases that affect more than one million patients worldwide, novel therapeutic approaches are in demand.  Aldeyra is committed to working with patients and physicians to attempt to ameliorate the unrelenting burden of retinitis pigmentosa, and we look forward to reporting top-line results of the Phase 2 clinical trial in the first half of this year.”