Applied Genetic Technologies Corporation (NASDAQ: AGTC), a gene therapy company, indicated that a treatment of a X-linked retinoschisis (XLRS) disorder has confirmed that interim six-month data from a Phase I/II clinical trial (rAAV2tYF-CB-hRS1) have no signs of clinical activity at six-months. AGTC announced that the company will not further develop the XLRS gene product.
X-linked retinoschisis is an inherited genetic disorder that typically affects the macular region and accounts for a leading cause of juvenile macular degeneration in males. The disorder is caused by mutations in the retinoschisis gene (RS1) leading to splitting of the inner retinal layers resulting in visual deterioration. A number of mis-sense and protein truncating mutations have been identified in the RS1 gene which encodes a 224 amino acid secretory retinal protein (retinoschisin), implicated in cell-cell interactions and cell adhesion. Loss of retinoschisin function may occur through interference of protein secretion, by prevention of octamerisation or by reducing function in the secreted octamerised protein. Patients may experience a progressive loss of vision between the ages of 5 and 10, while other symptoms include an inability to focus both eyes, roving and involuntary eye movements. There are no current treatment options available for XLRS and 35,000 patients in the US and Europe are estimated to suffer from the disease.
The clinical Phase I/II XLRS trial study was an open-label, dose escalation study to assess the safety and efficacy of intravitreal administration of the AAV-based gene therapy in patients diagnosed with XLRS caused by mutations in the RS1 gene. In short, there were no signs of clinical activity over the six-month interim analysis period while Sue Washer, President and CEO of AGCT, stated: “it is clear that the intravitreal injection used in our XLRS program created a challenge compared with our other clinical programs, all of which utilize a subretinal injection. While clinical plans for XLRP and ACHM (achromatopsia) are supported by robust data from naturally occurring large animal models, such models do not exist for XLRS. AGTC will benefit from our experience with the XLRS trial data because it strengthens our ability to effectively analyze and interpret a variety of important ophthalmic endpoints that have not commonly been used in inherited retinal diseases.”