Product information and disease description Product description Product information Pharmacology

Pharmacokinetics

5 evidence topics · 3 sources

Systemic exposure to the transgene product in nonhuman primates

“Serum aflibercept concentrations were below the lower limit of quantitation in all animals and at all time points in the 1 × 1011 vg/eye dose group.” (opens the source at this quote in a new tab)
“Low concentrations of aflibercept were detected in serum in 2 of 7 animals in both the 3 × 1011 and 1 × 1012 vg/eye dose groups; of these, only one animal in the 3 × 1011 vg/eye treatment group had quantifiable levels at more than one time point” (opens the source at this quote in a new tab)

Intraocular distribution assessed in nonhuman primates

“Cynomolgus macaques (age = 6 years) received bilateral IVT injections of 4D-150 1 × 1012 vg/eye.” (opens the source at this quote in a new tab)
“Secreted free aflibercept was detected in all tissue samples from all ocular compartments.” (opens the source at this quote in a new tab)

Vector shedding assessment in the PRISM clinical trial

“Vector Shedding sub-study: Approximately 15 subjects will receive an open-label IVT injection of 4D-150 to evaluate vector shedding.” (opens the source at this quote in a new tab)

Clinical pharmacokinetics, shedding results, and immunogenicity results in participants

No evidence found.

Cell-based infectivity assay for transduction-competent vector in serum

“Assessment of AAV vector shedding post-administration is required by regulatory health agencies and has traditionally been characterized by qPCR, a method that detects both transduced and encapsidated, potentially transduction-competent vector DNA, but does not discriminate between the two.” (opens the source at this quote in a new tab)
“The advantage of a cell-based infectivity assay is that it will only detect material that is potentially transduction competent.” (opens the source at this quote in a new tab)
“NAb(-) Serum Sensitivity: 3E4 vg/mL serum at MRD10” (opens the source at this quote in a new tab)
“NAb(+) Serum Sensitivity: 3E8 vg/mL serum at MRD10” (opens the source at this quote in a new tab)

Assay readout targeted to the transgene cassette

“The forward primer sits in the chicken beta actin Exon1 from the CAG promoter, while the reverse primer sits in the transgene (Tg) Exon 2.” (opens the source at this quote in a new tab)