X-linked retinitis pigmentosa (XLRP) is an inherited retinal disease that affects almost exclusively young males. This condition leads to progressive photoreceptor degeneration, causing symptoms such as difficulty seeing in low light, poor adaptation to changes in lighting, light sensitivity, and progressive loss of peripheral visual field. Patients with XLRP experience gradual visual field constriction, and by the age of 40–50, they typically develop “tunnel vision,” making it extremely difficult—if not impossible—to orient themselves and move around their environment.
X-linked retinitis pigmentosa is caused by mutations in the RPGR gene, which encodes the retinitis pigmentosa GTPase regulator. Although these mutations are rare and the disease affects approximately one in 40,000 young males, XLRP currently impacts more than 17,000 patients in the US and the EU5 countries (Italy, France, Germany, Spain, and the United Kingdom). Unfortunately, no therapeutic options are currently available, and both patients and specialists have long awaited a new opportunity for treatment through gene therapy.
Gene therapy aims to restore lost cellular function caused by a genetic defect by delivering a “healthy” copy of the mutated gene. Currently, the only approved gene therapy for retinitis pigmentosa is Spark Therapeutics’ Luxturna (voretigene neparvovec), which is indicated only for RP caused by biallelic mutations in the RPE65 gene. A specific gene therapy for XLRP caused by RPGR mutations has been developed by Beacon Therapeutics, which recently announced the launch of a Phase III clinical trial named VISTA.
The new gene therapy for X-linked retinitis pigmentosa uses AGTC-501 (laruparetigene zavoparvovec), a recombinant adeno-associated viral vector delivered through a single intravitreal injection. This therapy enables retinal cells to resume production of the full RPGR protein. Due to these characteristics, researchers believe AGTC-501 can preserve the function of both rod and cone photoreceptors, significantly improving quality of life for patients affected by XLRP.
Previous clinical trials of AGTC-501 (HORIZON and SKYLINE) have shown excellent results in terms of safety and efficacy, demonstrating good tolerability, no clinically significant adverse events, and improvements in retinal sensitivity and visual function. VISTA, a randomized, double-blind, multicenter Phase III trial, is designed to evaluate the safety, efficacy, and tolerability of a single subretinal injection of AGTC-501 at two dosage levels compared to an untreated control group. The study will enroll approximately 75 male patients between the ages of 12 and 50, all affected by X-linked retinitis pigmentosa caused by mutations in the RPGR gene. Initially, recruitment will begin in the United States and later expand globally.
The results obtained to date suggest that AGTC-501 may soon become the first gene therapy specifically approved for XLRP. These findings, along with those from the VISTA study, will support the submission of a Biologics License Application (BLA) in the United States and a Marketing Authorization Application (MAA) in the European Union.
The approval of AGTC-501 could revolutionize the prognosis for patients with X-linked retinitis pigmentosa, allowing for a meaningful degree of visual recovery or at least maintenance of vision in treated individuals. For this reason, the launch of the VISTA clinical trial marks a major milestone in the development of this new treatment and a true source of hope for the XLRP patient community, ophthalmologists, and all specialists in the field of retinal genetic degenerative diseases.
Dr. Jung Hee Levialdi Ghiron
Responsabile comunicazione scientifica Rome Vision Clinic
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