ADX-2191
A Novel Therapy for the Treatment of Retinitis Pigmentosa
Methotrexate, the active drug substance of ADX-2191, has long been utilized as both a chemotherapeutic agent and an immunomodulator. Intraocular methotrexate injections are the established standard of care for primary vitreoretinal lymphoma, a cancer affecting the posterior segment of the eye. Additionally, off-label use of methotrexate has become increasingly common in the management of proliferative vitreoretinopathy, posterior uveitis, and other retinal diseases.
ADX 2191 is specifically formulated for intraocular injection such that pH, viscosity, and solute concentration have been designed to be compatible with the vitreous humor, the fluid in the back of the eye. Further, ADX-2191 is a concentrated formulation of methotrexate that requires only a small injection volume, thereby mitigating injection site reflux and reducing the risk of corneal damage associated with off-label ocular methotrexate injections. The off-label intraocular injections of intravenous methotrexate for retinal diseases is an example of a practice known as compounding. Unlike compounded methotrexate, ADX 2191 possesses a higher density than the vitreous humor, enabling a localized and sustained concentration of methotrexate in close proximity to the retina.
Retinitis pigmentosa comprises a group of rare genetic diseases characterized by progressive photoreceptor degeneration and vision loss. All but one rare form of retinitis pigmentosa lacks a targeted drug treatment. In vivo preclinical research has identified the activity of methotrexate in inducing misfolded rhodopsin (a visual cycle protein) clearance, suggesting the potential of ADX-2191 as a disease-modifying therapy for retinitis pigmentosa subtypes associated with rhodopsin misfolding.
With an estimated global prevalence exceeding one million individuals, retinitis pigmentosa remains a significant cause of hereditary blindness. Mutations leading to rhodopsin misfolding account for approximately one-third of retinitis pigmentosa cases. The U.S. Food and Drug Administration has granted Orphan Drug Designation for the treatment of retinitis pigmentosa. Orphan Drug Designation facilitates the development of therapies for rare diseases by providing regulatory incentives, such as extended market exclusivity and financial support for clinical research.