Translational vision science & technology · 2025
Computational Fluid Dynamics Modeling of Intravitreal Ranibizumab Bolus Versus Subretinal ABBV-RGX-314 Transgene Product in Human Eyes.
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Park Jenny, Kazemi Mohammad, Tamhane Mitalee, Shen Jie
Аннотация
PURPOSE: ABBV-RGX-314 is being developed for neovascular age-related macular degeneration (nAMD). Computational fluid dynamics (CFDs) modeling in the eye enables simulation of drug distribution incorporating geometry and substructures of the eye across species. Given the similarity between ranibizumab and ABBV-RGX-314 transgene product (TP), ranibizumab intraocular pharmacokinetic (PK) data from literature were used to simulate intraocular drug distribution of ABBV-RGX-314 TP. This investigation aims to use CFD modeling to estimate retinal TP level based on aqueous humor (AH) TP level following subretinal (SR) injection of ABBV-RGX-314 in patients with nAMD.
METHODS: Ocular distribution of ranibizumab following a single intravitreal (IVT) injection was modeled in both monkey and human eyes independently. Following model validation, ABBV-RGX-314 TP distribution in human eyes was simulated following retinal transduction of ABBV-RGX-314.
RESULTS: Iterative simulations were performed to achieve similar AH ABBV-RGX-314 TP levels in patients with nAMD from phase I/IIa Study RGX-314-001. The CFD simulation estimated corresponding retinal TP concentrations of 1.86 to 5.50 µg/g at steady-state, which was assumed to be reached by 28 days and falls within the range of the estimated retinal ranibizumab trough retinal ranibizumab concentration (Ctrough; 0.718-5.37 µg/g) following monthly and every other month (EOM) dosing of 0.5 mg ranibizumab in patients with nAMD.
CONCLUSIONS: The current study results predict that the 2 pivotal trial ABBV-RGX-314 doses (6.4E10 and 1.3E11 genome copies/eye) are expected to achieve and maintain sufficient retinal ABBV-RGX-314 TP levels for the treatment of nAMD.
TRANSLATIONAL RELEVANCE: CFD modeling effectively bridges limited human ocular PK data with rich preclinical data, supporting model-informed drug development (MIDD) for clinical dose selection.
METHODS: Ocular distribution of ranibizumab following a single intravitreal (IVT) injection was modeled in both monkey and human eyes independently. Following model validation, ABBV-RGX-314 TP distribution in human eyes was simulated following retinal transduction of ABBV-RGX-314.
RESULTS: Iterative simulations were performed to achieve similar AH ABBV-RGX-314 TP levels in patients with nAMD from phase I/IIa Study RGX-314-001. The CFD simulation estimated corresponding retinal TP concentrations of 1.86 to 5.50 µg/g at steady-state, which was assumed to be reached by 28 days and falls within the range of the estimated retinal ranibizumab trough retinal ranibizumab concentration (Ctrough; 0.718-5.37 µg/g) following monthly and every other month (EOM) dosing of 0.5 mg ranibizumab in patients with nAMD.
CONCLUSIONS: The current study results predict that the 2 pivotal trial ABBV-RGX-314 doses (6.4E10 and 1.3E11 genome copies/eye) are expected to achieve and maintain sufficient retinal ABBV-RGX-314 TP levels for the treatment of nAMD.
TRANSLATIONAL RELEVANCE: CFD modeling effectively bridges limited human ocular PK data with rich preclinical data, supporting model-informed drug development (MIDD) for clinical dose selection.