The latest genetic research from this summer’s retina conferences
Gene therapy was a major topic at the 2024 EURETINA and Retina Society meetings
In September, ophthalmologists at the European Society of Retina Specialists (EURETINA) and Retina Society meetings presented on a number of innovative gene therapies. We have highlighted two presentations for you here, and invite you to check out the full suite of conference coverage available via the Eye Care Network.
Ophthalmologists at EURETINA and Retina Society meetings presented on a number of innovative gene therapies. Image credit: ©Iftikhar alam – stock.adobe.com
Subretinal gene therapy for Bothnia dystrophy
Patients with Bothnia dystrophy benefited from subretinal administration of AAV8-RLBP1 gene therapy, which was considered safe and well tolerated, according to lead author Anders Kvanta, MD, from St. Erik Eye Hospital, Karolinska Institute, Stockholm. Dr Kvanta presented these findings at the EURETINA meeting in Barcelona, Spain.
Bothnia dystrophy generally presents in early childhood; patients have night blindness, progressive visual loss and later, legal blindness.
Dr Kvanta and colleagues conducted an open-label, dose-escalating, first-in-human, phase 1/2 study that included 12 patients with very delayed dark adaptation (DA) who received increasing subretinal AAV8-RLBP1 doses (5 x 109 to
1 x1011 vg/eye). Ocular and systemic safety; DA kinetics, the primary efficacy end-point; and other light- and dark-adapted visual function measures were assessed. Following overnight DA, recovery to full-field stimuli was assessed over 6 hours.
DA recovered with short-wavelength stimuli (450 nm) and improved in eight of 12 patients 1 hour after bleaching light, 11 patients at 2 hours, and 9 patients at 3 hours. The improvements were sustained to the latest follow-up. Patients also reported improvement in daily activities. The prevalence of baseline retinitis punctata albescens decreased rapidly with the improved DA parameters in the treated eyes of three patients.
Read the full article and see more EURETINA coverage
Intravitreal gene therapy for neovascular AMD
At the Retina Society meeting in Lisbon, Portugal, David A. Eichenbaum, MD, of Retina Vitreous Associates of Florida, USA, presented on neovascular age-related macular degeneration (nAMD). Speaking to Ophthalmology Times, he highlighted interim results from the PRISM (NCT05197270) phase 1/2 trial evaluating intravitreal 4D-150 in adults with nAMD. 4D-150, from 4D Molecular Therapeutics, comprises an intravitreal vector, R100, and a transgene payload that expresses both aflibercept and a VEGF-C inhibitory RNA interference. It is designed for single low-dose delivery.
Dr Eichenbaum the PRISM phase 1/2 trial ”enrolled a broad wet AMD population with a wide range of disease activity and antiangiogenic treatment burden in the phase 2 interim results.” The week 24 results showed 4D-1500 at 3E10 was safe and well tolerated, with no serious ocular adverse events or clinically significant inflammation.
The most exciting outcome was “durable clinical activity,” Dr Eichenbaum said. “In Phase 2, there was an almost 90% reduction in the annualised anti-VEGF injection treatment burden, stable visual acuity and sustained reduction in central subfield thickness [CST] stabilisation and freedom from CST fluctuations,” he said. Additionally, 84% of patients received zero or one supplemental aflibercept injection, with 63% of patients injection-free through 24 weeks.
The Phase 3 trial, informed by prior PRISM trial results, is slated to begin in early 2025, Dr Eichenbaum noted. The 3E10 vg/eye dose has been selected for the upcoming Phase 3 trial.
