Landon Rohowetz, MD
Bascom Palmer Eye Institute
Saturday of ASRS kicked off with the Wet AMD Symposium 1 moderated by Jeffrey Heier, MD, and Aleksandra Rachitskaya, MD. The talks were engaging and covered topics from high-dose aflibercept to gene editing to clinical trial setup.
The first four presentations outlined data from the PULSAR trial, which is the Phase 3 trial comparing the safety and efficacy of intravitreal aflibercept 8 mg every 12 or 16 weeks with aflibercept 2 mg every 8 weeks. Jignesh Patel, MD, FRCOphth, was first to present and demonstrated that the observed mean change in baseline best corrected visual acuity (BCVA) was similar between the three aforementioned groups. More than three-quarters of patients in the every 12 or 16 week groups were maintained at their respective intervals at 1 year. The 8 mg group demonstrated superior drying at week 16 compared to the 2 mg group. Furthermore, the rate of adverse events was similar between the two groups.
David Chow, MD, FRCS(C) then presented a post hoc analysis of the PULSAR trial that sought to identify baseline characteristics that predict patients who need shortened treatment intervals. The post hoc analysis evaluated the following baseline characteristics: BCVA, central subfield thickness, and choroidal neovascularization (CNV) size. Ultimately, their data demonstrated that none of these baseline characteristics were predictive of the need for treatment intervals shorter than every 12 or 16 weeks.
David Wong, MD, FCRS(C), FASRS presented a subgroup analysis of patients with polypoidal choroidal vasculopathy (PCV) in the PULSAR trial. This analysis demonstrated that the outcomes in the PCV subgroup were similar to those of the overall study population, with most patients in the 8 mg group being able to maintain intervals of every 12 or 16 week intervals.
Finally, Keyvan Koushan, MD, FRCSC, presented a subgroup analysis of treatment-naïve patients in the PULSAR trial. He demonstrated that visual acuity outcomes were similar between the 2 mg and 8 mg groups and outcomes were not influenced by baseline BCVA, central retinal thickness (CRT), or CNV type.
To kick off part 2 of this symposium, Min Sagong, MD, PhD, presented data from a Phase 3 trial comparing aflibercept to its biosimilar, SB15, administered every 8 weeks following an initial loading regimen. This trial demonstrated that changes in mean BCVA and mean central subfield thickness (CST) were comparable between groups up to week 56. Moreover, the rate and incidence of adverse events were similar between groups. Finally, the trial showed that switching from aflibercept to SB15 was safe and effective in patients who were re-randomized to switch therapies at week 32.
Marco Zarbin, MD, PhD, presented a study evaluating the impact of disease activity criteria on dosing interval assignment in clinical trial patients with wet AMD. The study demonstrated that altering clinical trial disease activity criteria can have a significant impact on dosing interval determination. As an example, if the PULSAR trial disease activity criteria was applied to the TENAYA/LUCERNE data, 96% of participants would have achieved at least an every 12 week treatment schedule compared to the 78% reported in the study.
Christine Kay, MD, presented data from the PRISM study, an ongoing dose exploration and randomized expansion study of 4D-150, an intravitreal AAV vector carrying a transgene payload that expresses aflibercept and a inhibitory RNAi against VEGF-C. A 96.7% overall reduction in the mean annualized anti-VEGF injection rate was observed after a single intravitreal injection of 4D-150. Higher doses were associated with lower rates of supplemental aflibercept injection. The treatment was safe and well-tolerated with no dose-limiting toxicities or serious adverse events, and no clinically significant intraocular inflammation.
Finally, Glenn Yiu, MD, PhD, presented his research on the use of CRISPR gene-editing for the treatment of wet AMD. In this preclinical study, an AAV-mediated CRISPR-based gene-editing therapy targeting VEGFA was administered to mice and monkeys with laser-induced choroidal neovascularization. He demonstrated that this treatment was effective at reducing VEGF levels and suppressing choroidal neovascularization in mouse eyes but led to retinal thinning and photoreceptor disruption in non-human primates.
The symposium was overall a great success, covering a variety of late-breaking topics and including interactive discussion that will surely impact how retina specialists care for patients worldwide.