ASRS 2023: Late-breaking Clinical Trials for AMD and DR

Sandra Hoyek, MD
Massachusetts Eye and Ear
Boston, MA

On August 1st, 2023, the final session of ASRS 2023 was moderated by J. Michael Jumper, MD, FASRS and Robin Vora, MD focused on late-breaking studies related to age-related macular degeneration (AMD).

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Dr. Lisa Olmos de Koo, MD, MBA presented the 48-month visual acuity results of subretinal implantation of the PRIMA bionic vision system. This system is designed to partially restore vision in patients with geographic atrophy (GA) due to AMD. This prospective, non-randomized, non-masked feasibility study included 5 patients with GA involving the foveal center and no central visual perception. The implant was successfully placed under the central retina with, although one patient developed inferior displacement of implant in the immediate postoperative period (also observed in a previous series). Adverse events included 2 cases of intraocular pressure elevation, 1 case of superotemporal retinal detachment and a case of choroidal neovascular membrane. However, the visual acuity improvement was clinically meaningful. Dr. Olmos concluded that the subretinal implantation of PRIMA in subjects with GA due to AMD is potentially feasible and safe, with no reduction in natural peripheral visual acuity. A plan for a US clinical trial is currently underway.

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Dr. David Eichenbaum, MD, FASRS shared the results of the GALLEGO phase 2 randomized trial investigating intravitreal injection (ITV) of galegenimab, an anti-HTRA1 anti-binding fragment, in AMD patients with GA. The study evaluated two dosing regimens, 20 mg of galegenimab every 4 weeks (Q4W) and every 8 weeks (Q8W). Results showed no statistically significant difference in mean change in GA area compared to pooled sham arms up to Week 72. The treatment exhibited a notable rate of intraocular inflammation (16/224, 7.1%), most of which resolved with topical steroids. Of note, no cases of occlusive retinal vasculitis were reported. Throughout the study period, the rate of anti-drug-antibodies increased from 3% to 29%. Therefore, a monitoring committee recommended early discontinuation of the study due to benefit/risk analysis. During the panel discussion, emphasis was placed on the significance of reporting negative results.

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Dr. Robert Avery, MD presented the results of a randomized, double-masked US-based clinical trial comparing the duration of the biological activity of OTX-TKI, a sustained-release tyrosine kinase inhibitor implant, to aflibercept Q8W in patients with previously treated, controlled wet AMD. The study enrolled 16 subjects in the OTX-TKI group and 5 subjects in the aflibercept group. OTX-TKI demonstrated similar maintenance of visual acuity and central subfield thickness to aflibercept over a 12-month period, resulting in an 89% reduction in treatment burden. Safety data indicated that OTX-TKI was generally well-tolerated, with no drug-related serious adverse events reported. The trial suggests OTX-TKI as a potential treatment option for neovascular AMD, offering durability lasting between 9 to 12 months after a single injection.

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Dr. Dennis Marcus, MD, reported new data on the PDS (a continuous drug delivery system) for treating diabetic macular edema (DME) and diabetic retinopathy (DR). The ongoing phase 3 randomized trials, PAGODA (PDS Q24W vs IVT ranibizumab (RBZ) Q4W) and PAVILION (PDS Q36W vs control, defined as observation plus supplemental IVT RBZ as required), both met their primary endpoints. The PDS demonstrated noninferiority to standard IVT RBZ in terms of visual acuity improvement and absence of DME. In the PAVILION trial, PDS showed superiority over the control group in achieving significant improvements in DR severity and preventing center-involved DME. The PDS was well-tolerated with no new safety signals observed. It holds the potential to offer functional and anatomical benefits, prevent disease progression, and reduce the frequency of injections required. Dr. Marcus mentioned that modifications were made to the implant and refill needles to address the septum dislodgment concern, which has not led to safety issues thus far. The plan is to resume clinical trials and engage in FDA discussions to reintroduce SUSVIMO (PDS with ranibizumab) to the commercial market.

The meeting concluded with an announcement about the upcoming ASRS annual meeting that will be held in Stockholm, Sweden from July 17 to 20, 2024.