Ophthalmology science · 2026
Pharmacodynamics of Free VEGF After Treatment with the Port Delivery Platform with Ranibizumab in Patients with Neovascular Age-Related Macular Degeneration.
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Maass Katie F, Maia Mauricio, Gune Shamika, Chang Michael C
Аннотация
OBJECTIVE: To evaluate the pharmacodynamics of aqueous humor (AH) free VEGF concentrations after treatment with the Port Delivery Platform with ranibizumab (PDS) in patients with neovascular age-related macular degeneration (nAMD).
DESIGN: Pharmacokinetic and pharmacodynamic analyses from the phase III Archway (NCT03677934) and phase II Ladder (NCT02510794) trials.
PARTICIPANTS: Patients with treatment-responsive nAMD.
METHODS: In Archway, patients received PDS 100 mg/mL with refills every 24 weeks (Q24W) or intravitreal ranibizumab 0.5 mg every 4 weeks (Q4W) for 96 weeks. In Ladder, patients received PDS 10, 40, or 100 mg/mL with refills based on protocol-defined criteria or intravitreal ranibizumab 0.5 mg Q4W. Aqueous humor samples were collected throughout the trials (PDS arms only in Ladder) in a subset of patients.
MAIN OUTCOME MEASURES: Aqueous humor ranibizumab and free VEGF concentrations.
RESULTS: Archway analyses included 1149 AH samples from 215 patients. Ladder analyses included 109 AH samples from 47 patients. Aqueous humor ranibizumab concentrations after treatment with the PDS were consistent with the PDS implant release rate. Median AH free VEGF concentrations at randomization (on average 3 weeks after intravitreal ranibizumab injection) were 8.46 and 7.26 pg/mL in the PDS 100 mg/mL and intravitreal ranibizumab Q4W arms, respectively. Throughout the trial, AH free VEGF concentrations remained suppressed in both arms relative to previously reported values from treatment-naïve patients, and AH free VEGF concentrations 24 weeks after treatment with PDS 100 mg/mL Q24W were similar to or lower than those 4 weeks after treatment with intravitreal ranibizumab. In Ladder, analysis of limited samples suggests there was a tendency for a delayed loss of AH free VEGF suppression with increasing ranibizumab dose. Below AH ranibizumab concentrations of ∼106 pg/mL, there was a negative correlation between AH free VEGF and AH ranibizumab concentration. There were no correlations between AH free VEGF concentrations and clinical outcomes in either arm, including change from baseline in best-corrected visual acuity and central subfield thickness at week 96.
CONCLUSIONS: These findings demonstrate that PDS 100 mg/mL Q24W suppresses AH free VEGF throughout the entire 24-week refill-exchange interval and to an extent similar to that at 4 weeks after intravitreal ranibizumab.
FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
DESIGN: Pharmacokinetic and pharmacodynamic analyses from the phase III Archway (NCT03677934) and phase II Ladder (NCT02510794) trials.
PARTICIPANTS: Patients with treatment-responsive nAMD.
METHODS: In Archway, patients received PDS 100 mg/mL with refills every 24 weeks (Q24W) or intravitreal ranibizumab 0.5 mg every 4 weeks (Q4W) for 96 weeks. In Ladder, patients received PDS 10, 40, or 100 mg/mL with refills based on protocol-defined criteria or intravitreal ranibizumab 0.5 mg Q4W. Aqueous humor samples were collected throughout the trials (PDS arms only in Ladder) in a subset of patients.
MAIN OUTCOME MEASURES: Aqueous humor ranibizumab and free VEGF concentrations.
RESULTS: Archway analyses included 1149 AH samples from 215 patients. Ladder analyses included 109 AH samples from 47 patients. Aqueous humor ranibizumab concentrations after treatment with the PDS were consistent with the PDS implant release rate. Median AH free VEGF concentrations at randomization (on average 3 weeks after intravitreal ranibizumab injection) were 8.46 and 7.26 pg/mL in the PDS 100 mg/mL and intravitreal ranibizumab Q4W arms, respectively. Throughout the trial, AH free VEGF concentrations remained suppressed in both arms relative to previously reported values from treatment-naïve patients, and AH free VEGF concentrations 24 weeks after treatment with PDS 100 mg/mL Q24W were similar to or lower than those 4 weeks after treatment with intravitreal ranibizumab. In Ladder, analysis of limited samples suggests there was a tendency for a delayed loss of AH free VEGF suppression with increasing ranibizumab dose. Below AH ranibizumab concentrations of ∼106 pg/mL, there was a negative correlation between AH free VEGF and AH ranibizumab concentration. There were no correlations between AH free VEGF concentrations and clinical outcomes in either arm, including change from baseline in best-corrected visual acuity and central subfield thickness at week 96.
CONCLUSIONS: These findings demonstrate that PDS 100 mg/mL Q24W suppresses AH free VEGF throughout the entire 24-week refill-exchange interval and to an extent similar to that at 4 weeks after intravitreal ranibizumab.
FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.