Aldeyra Therapeutics, Inc. (NASDAQ: ALDX), a clinical stage company based in Lexington, Massachusetts, has reported the initiation 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.
As well known, 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.
According to the announcement on the Phase 2 by the company, a single-center, open-label clinical trial will evaluate the safety and tolerability of ADX-2191 in patients diagnosed with RP due to mutations of the rhodopsin gene, including the P23H gene mutation. The trial is expected to enroll eight patients, with four patients receiving monthly and four patients receiving twice-monthly intravitreal injections of ADX-2191 over a period of three months. The trial is being conducted at Duke University Medical Center in Durham, North Carolina and the top-line results are expected in the second half of 2022. Commenting on the trial initiation, Todd C. Brady, M.D., Ph.D., President and Chief Executive Officer of Aldeyra stated, “ADX-2191 represents a novel approach for the treatment of patients with retinitis pigmentosa, an incurable, sight-threatening condition. We are excited about the opportunity to advance our ADX-2191 retinal program across a variety of rare and underserved diseases.”