Abstract
Purpose :
The Port Delivery System with ranibizumab (PDS) is a drug delivery system approved in the United States for neovascular age-related macular degeneration (nAMD). Following surgical implantation via the pars plana, the PDS allows for continuous intravitreal delivery of a customized formulation of the anti–vascular endothelial growth factor (VEGF) ranibizumab. In the phase 3 Archway trial of the PDS for nAMD (NCT03677934), aqueous humor (AH) samples were collected to characterize pharmacokinetics and pharmacodynamics of ranibizumab delivered via the PDS and intravitreal injection.
Methods :
Archway assessed PDS 100 mg/mL and fixed refill-exchanges every 24 weeks (wks) vs monthly intravitreal ranibizumab 0.5 mg injections. All patients had ≥ 3 anti-VEGF intravitreal injections before screening and an intravitreal ranibizumab 0.5 mg injection at end of screening, 21–28 days before baseline (BL). Optional AH samples, each collected predose, were obtained and analyzed at BL and wks 24, 28, 48, and 52. Ranibizumab and free VEGF AH concentrations were measured using validated enzyme-linked immunosorbent assays with lower limits of quantitation of 20 ng/mL and 1.46 pg/mL, respectively. Significance was tested via Wilcoxon rank test with Bonferroni multiplicity correction.
Results :
Optional AH samples were available for 102/248 and 65/167 patients at BL in the PDS and monthly ranibizumab arms, respectively. At BL, median AH ranibizumab and free VEGF concentrations (Table 1) were similar in both arms. At post-BL visits, ranibizumab concentrations were higher and free VEGF concentrations were lower in the PDS arm at 4 and 24 wks since dose, versus 4 wks since ranibizumab injection (PDS vs monthly ranibizumab, P<0.01 at each timepoint). In the PDS arm, free VEGF concentrations were similar at 4 and 24 wks since dose, indicating sustained free VEGF suppression throughout the 24-wk refill interval with the PDS. No correlations were observed between free VEGF concentrations and maintenance of BL best-corrected visual acuity or central subfield thickness at wk 36/40 in either arm.
Conclusions :
The PDS delivered a more sustained concentration of ranibizumab versus monthly injections, resulting in improved longitudinal suppression of VEGF in AH.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.