Applied Genetic Technologies Offers Data Evaluating Novel AAV-Based Gene Therapy as Potential Treatment for LCA, SECORD

Applied Genetic Technologies Corporation AGTC, a biotechnology company conducting human clinical trials of adeno-associated virus (AAV)-based gene therapies for the treatment of rare diseases, today announced data evaluating an experimental recombinant AAV vector gene delivery in patients with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD), two related retinal diseases caused by mutations in the RPE65 gene that cause severe loss of vision in infancy. Results from the study, entitled "Results at 2 Years after Gene Therapy for RPE65-deficient Leber Congenital Amaurosis and Severe Early-Childhood Onset Retinal Dystrophy," were published online in the peer-reviewed journal Ophthalmology and will appear in the April print issue of the journal. "LCA and SECORD are serious retinal degenerative conditions with no current treatments that can lead to total blindness and significantly impair quality of life in affected individuals," said contributing study author Jeff Chulay, M.D., DTM&H, Vice President and Chief Medical Officer of AGTC. "We are encouraged by these results demonstrating that administration of a novel AAV-based gene therapy can improve several measures of abnormal visual function in patients affected by these disorders." The study was conducted at Oregon Health and Science University (OHSU) Casey Eye Institute (CEI) and University of Massachusetts. The study enrolled eight adults and four children with LCA or SECORD who received a subretinal injection of a recombinant AAV expressing RPE65 (rAAV2-CB-hRPE65) at one of two dose levels in the poorer seeing eye. All subjects then underwent serial assessments of visual function and adverse events during two-year clinical follow-up to evaluate safety and efficacy parameters. All subjects tolerated the surgery and study agent administration with no treatment-related serious adverse events reported. In the treated eye, best-corrected visual acuity (BCVA) increased in five subjects, static perimetry hill of vision measurements for the central 30° of the visual field increased in six subjects, total visual field hill of vision measurements increased in five subjects, and kinetic visual field area improved in three subjects. One study participant had a decrease in BCVA and two subjects had a decrease in kinetic visual field area. Common adverse events associated with the injection included subconjunctival hemorrhage in eight subjects and ocular hyperemia (redness) in five subjects. The investigators concluded that the treatment with rAAV2-CB-hRPE65 was not associated with serious adverse events and improvement in one or more measures of visual function was observed in 9 of 12 (75 percent) subjects. "While AGTC has made a strategic decision to focus on commercializing treatments for other orphan indications, these results are promising and add to previously published proof of concept data supporting gene therapy applications for inherited retinal diseases," noted Sue Washer, President and CEO of AGTC. "We have recently achieved several important clinical and regulatory milestones for the product candidates in our pipeline, including our lead product candidates for the treatment of the orphan indications X-linked retinoschisis and achromatopsia, and look forward to announcing continued progress in our primary clinical programs in the coming months."