Sneha Padidam, MD
Vitreoretinal surgical fellow
Retina Group of Washington, Washington, D.C.
Dr. David Eichenbaum of Retina Vitreous Associates of Florida presented the results of a Phase 1 study evaluating the safety and tolerability of intravitreal injections of NGM621, a monoclonal antibody, for the treatment of geographic atrophy (GA) resulting from age-related macular degeneration (ARMD).
Overactivation of the complement cascade is thought to contribute to the pathogenesis of GA in ARMD. NGM621, a humanized IgG1 monoclonal antibody, inhibits complement C3 cleavage, preventing downstream activation of the complement cascade.
This Phase 1 study evaluated the safety and tolerability of the NGM621 administered via intravitreal injection and assessed its pharmacokinetic and pharmacodynamic profiles. Inclusion criteria were patients ≥ 50 years of age with GA secondary to ARMD in at least one eye, GA lesion size ≥2.5mm2, BCVA 20/80 to 20/400 in study eye, and no history or evidence of choroidal neovascularization in either eye. Fifteen eyes of 15 patients were included in the study. In the single dose cohort (n=9) intravitreal NGM621 (2, 7.5, 15 mg) were administered to 3 patients per dose. In the multidose cohort (n=6), patients received two 15 mg doses of intravitreal NGM621 4 weeks apart. 80% of eyes had a unifocal lesion and 87% had advanced stage geographic with foveal involving lesions. The patients were followed for 12 weeks in total.
All 15 patients completed the study and no vision related safety issues such as endophthalmitis, inflammation, or choroidal neovascularization occurred. No serious ocular or systemic adverse events attributed to the study drug occurred. Standard injection related adverse events such as pruritis and subconjunctival hemorrhage did occur. Mean BCVA and mean GA lesion area were stable over the 12-week period in all 4 dosing cohorts. Intraocular pressure was not meaningfully elevated over time. The serum PK was linear and dose proportional with low accumulation after a second dose 4 weeks later. After intravitreal injection of NGM612, the serum exposure was below concentrations that produce systemic complement inhibition. Ocular PK/PD modeling supports a 15 mg dosing interval of up to 8 weeks apart. Building on the Phase 1 data, NGM621 is now being studied in the multicenter double- masked Phase 2 CATALINA study of NGM621 injection vs. sham injection with every 4-week or every 8-week dosing.
