REGENXBIO announced it completed dosing across all five cohorts in the Phase I/IIa clinical trial of RGX-314 for the treatment of wet age-related macular degeneration (wet AMD).
"We are excited to announce this important clinical milestone as we continue to drive the development of RGX-314 as a potential one-time gene therapy for patients with wet AMD," said Steve Pakola, M.D., Chief Medical Officer of REGENXBIO. "Patients with wet AMD require intravitreal injections every four to 12 weeks, on average, with the current standard of care. We were pleased to report durable treatment response from Cohort 3 of the RGX-314 Phase I/IIa trial for wet AMD at one year after a single administration of RGX-314 in a heavily pre-treated patient population in our interim trial update earlier this month," added Dr. Pakola. "We look forward to providing top-line data, including from Cohorts 4 and 5, in the Phase I/IIa trial by the end of the year."
Eight leading retinal surgery centers across the United States are participating in the Phase I/IIa trial of RGX-314, designed to evaluate the safety and tolerability of RGX-314 as a one-time therapy for patients with wet AMD who were previously treated with anti-vascular endothelial growth factor (VEGF) injections. The trial includes 42 dosed subjects across five escalating dose cohorts. Each subject received a single dose of RGX-314 administered by subretinal delivery.
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"The sustained clinical durability of effect seen one year after one-time administration of RGX-314 in Cohort 3 demonstrates the potential of RGX-314 to provide foundational anti-VEGF therapy that may sustain vision gains and alleviate treatment burden for millions of patients suffering from wet AMD," added Robert Avery, M.D., trial investigator and retina surgeon from California Retina Consultants.
REGENXBIO is planning to initiate a Phase IIb trial in wet AMD by the end of 2019 based on the Phase I/IIa trial data and expand clinical development of RGX-314 by filing an Investigational New Drug (IND) application for diabetic retinopathy (DR) in the second half of 2019.
RGX‑314 is being evaluated in a Phase I/IIa, multi-center, open-label, multiple-cohort, dose‑escalation study in adult subjects with wet AMD in the United States. The study includes subjects previously treated for wet AMD who are responsive to anti-VEGF therapy. The study is designed to evaluate five escalating doses of RGX-314, with six subjects in the first three dose cohorts and 12 subjects in the fourth and fifth dose cohorts. Secondary endpoints include visual acuity, retinal thickness on spectral domain optical coherence tomography (SD‑OCT), ocular RGX-314 protein expression, and the need for additional anti-VEGF therapy. Following completion of the primary study period, subjects enter a follow-up period and will continue to be assessed until week 106 for long-term safety and durability of effect.
Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. Wet AMD is a significant cause of vision loss in the United States, Europe and Japan, with up to 2 million people living with wet AMD in these geographies alone. Current anti-VEGF therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients. These therapies, however, require life-long intraocular injections, typically repeated every four to 12 weeks in frequency, to maintain efficacy. Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time.
RGX-314 is being developed as a potential one-time subretinal treatment for wet AMD and DR. It includes the NAV AAV8 vector encoding an antibody fragment which inhibits VEGF, preventing the proliferation of leaky blood vessels which lead to retinal fluid accumulation and vision loss. In preclinical animal models to evaluate anti-VEGF therapies, prevention of disease progression was observed after a single subretinal dose of RGX-314.