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Peter A Campochiaro, Shamika Gune, Mauricio Maia, Katie Maass; Pharmacokinetic (PK) Profile of the Port Delivery System with Ranibizumab (PDS) in the Phase 2 Ladder Trial. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1157.
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The PDS is an investigational drug delivery system that includes a pars plana implant for continuous the delivery of a specialized formulation of ranibizumab into the vitreous. Ranibizumab release from the implant follows first-order kinetics and is mediated by passive diffusion. In the phase 2 Ladder trial (NCT02510794) in patients with neovascular AMD (nAMD; N=220), serum samples were collected to characterize the PK of ranibizumab after the initial fill and subsequent refills of the PDS implant.
Serum PK samples were collected from patients in the PDS 10, 40, and 100 mg/mL arms on day 1 at least 60 minutes following implant insertion, at 1, 7, and 14 days after implant insertion, at each monthly study visit, and at 1 and 7 days after each refill. Serum samples were also collected from patients in the monthly intravitreal ranibizumab 0.5 mg arm at randomization, months 1, 3, 6, and 9, and at the final study visit to assess Ctrough levels. Serum ranibizumab concentrations were measured using a validated enzyme-linked immunosorbent assay with a lower limit of quantification of 15 pg/mL.
Independent of the timing and number of refills, the median serum ranibizumab concentrations at Month 9 were 27.3, 111, and 235 pg/mL in the PDS 10, 40, and 100 mg/mL arms, respectively. The median serum ranibizumab concentration at Ctrough at Month 9 in the monthly intravitreal ranibizumab arm was 56.1 pg/mL. Following implant insertion and before first refill, the geometric mean (coefficient of variation) of the serum ranibizumab concentrations were 243 (146%), 160 (155%), 101 (137%), 50.8 (108%) pg/mL at months 6, 9, 12, and 16 respectively, in PDS 100 mg/mL patients who never received ranibizumab injections in study or fellow eye after implant insertion or intravitreal bevacizumab treatment. For all three PDS arms, the serum concentration versus time profiles were consistent following implant insertion and across multiple refills.
The PDS implant continues to release ranibizumab for an extended period of time, including through Month 16 in the PDS 100 mg/mL arm. These findings explain the median time to first refill of 15.8 months observed in PDS 100 mg/mL patients in the Ladder trial, which was associated with sustained visual gains that were comparable to monthly intravitreal ranibizumab.
This is a 2020 ARVO Annual Meeting abstract.
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