Several papers presented at AAO 2019 discussed different outcomes for treatments of age-related macular degeneration (AMD).
The first paper, “Phase 1 Single and Multiple Ascending Dose Studies of LBS-008, a Novel Therapy for Stargardt Disease and Dry AMD,” is the first human study to evaluate safety, pharmacokinetics (PK), and pharmacodynamics (PD) of oral LBS-008, according to the researchers. The study included 40 patients in five cohorts for the single ascending dose (SAD) arm, and 32 patients in four cohorts for the multiple ascending dose (MAD) arm. In each cohort, six patients received LBS-008 and two received placebo. The SAD doses were 25 mg, 50 mg, 100 mg, 200 mg, and 400 mg, and the MAD doses were 10 mg, 25 mg, 50 mg, and 100 mg, for 14 days. Outcomes included serum RBP4 and retinol levels. LBS-008 use resulted in good safety, PK, and PD outcomes; no dose-limiting toxicities occurred in patients who completed the trial, and RBP4 lowering reached 90%.
The second paper, “Phase 1/2a Study of Subretinally Transplanted Human Embryonic Stem Cell-Derived RPE Cells in Advanced Dry-Form AMD Patients,” reported interim data on patients partaking in the “Phase I/IIa Dose Escalation Safety and Efficacy Study of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium Cells Transplanted Subretinally in Patients With Advanced Dry-Form Age-Related Macular Degeneration (Geographic Atrophy)” clinical trial. In this study, patients with advanced dry AMD (n = 15) underwent transplant to receive human embryonic stem cell-derived retinal pigment epithelial cells (OpRegen). Two routes of administration were used: pars plana vitrectomy or injection via the suprachoroidal route. Functional/structural outcomes were evaluated with best corrected visual acuity (BCVA) and imaging. The researchers reported positive interim outcomes and no unexpected adverse events (AEs). OpRegen was associated with subretinal pigmentation, decreased drusen density, irregular reflectance above atrophy areas, and ellipsoid zone changes as evidenced through optical coherence tomography imaging.
The third paper, “Ziv-Aflibercept Efficacy in Better Regulating AMD: 52-Week Results of the ZEBRA Study,” compared ziv-aflibercept to other antivascular endothelial growth factor (anti-VEGF) agents in neovascular AMD patients. Eligible patients were required to have active disease, a history of anti-VEGF treatment, and BCVA < 20/250. Patients were randomized to two groups: one group received 1.25 mg/0.05mL intravitreal ziv-aflibercept (treatment group), and the other continued their current treatment plan (control group). Final analysis included 56 patients. Mean baseline BCVA at one year was 1.58 ± 0.42 logMAR in the control group and 1.76 ± 0.32 logMAR in the treatment arm; mean changes in BCVA were 0.07 and 0.01 logMAR, respectively. Baseline central foveal thickness (CFT) was 261 ± 81 µm in the control group and 242 ± 79 µm in the treatment group; mean changes in CFT were 7 and −3 µm, respectively. No AEs occurred in either group. The authors concluded that ziv-aflibercept is anatomically and functionally noninferior to other anti-VEGF agents and may be a cost-effective option compared to aflibercept and could serve as a second-line therapy for eyes that do not respond to bevacizumab.