REGENXBIO Inc. (Nasdaq: RGNX), a clinical-stage biotechnology company has reported that 42 patients have been enrolled in the RGX- 314-001 study (NCT03066258) with up to 3 years of follow-up dosed in the “AAVIATE” trial, a Phase II trial to evaluate the suprachoroidal delivery of RGX-314 for the treatment of wet age-related macular degeneration (wet AMD). The study used a randomized, dose-escalation trial designed to evaluate the efficacy, safety and tolerability of RGX-314 gene therapy in subjects with nAMD. Efficacy will be the primary focus of the study and participants will be evaluated for safety and tolerability. therapy vector carrying a coding sequence for a soluble anti-VEGF protein. The company proposes RGX-314 to be a long-term, stable delivery treatment for a 1 time gene therapy, thereby potentially to reduce the treatment burden of currently available therapies for other marketed anti-VEFG treatments.
RGX-314 is being developed for wet AMD and diabetic retinopathy using an AAV8 vector encoding an antibody fragment designed to inhibit vascular endothelial growth factor (VEGF). According to the company, two separate routes of administration of RGX-314 use a standardized subretinal delivery procedure as well as delivery to the suprachoroidal space. A microinjector medical device from Clearside Biomedical, Inc. is aimed to deliver gene therapy treatment to the suprachoroidal space of the eye. The primary outcome of the study across 5 US centres is aimed to evaluate the mean change in BCVA for RGX-314 compared with ranibizumab monthly. The trial enrolled approximately >40 patients with severe wet AMD across two cohorts. Patients in each cohort were randomized to receive RGX-314 versus monthly 0.5 mg ranibizumab intravitreal injection at a 3:1 ratio, and two dose levels of RGX-314 evaluated: 2.5×1011 GC/eye and 5×1011 GC/eye. Patients had proposed not receive prophylactic immune suppressive corticosteroid therapy before or after administration of RGX-314.
Following the interim results. REGENXBIO reported that the 42 patients tolerated well the treatment with stable to improved visual acuity (VA). Dr. Allen C. Ho, MD, Professor of Ophthalmology at Wills Eye Hospital in Philadelphia, and Thomas Jefferson University in Plymouth Meeting, Pennsylvania, commented that “RGX-314 continues to be generally well tolerated across all doses. Importantly, no clinically determined immune responses, drug-related ocular inflammation, or postsurgical inflammation were seen beyond what is expected following routine vitrectomy.” While all formalised results are to be presented in due course, secondary outcome measures will be focusing on safety measurements, BCVA, CRT as measured by SD-OCT, the mean number of rescue injections and the area of CNV and leakage measured by FA.