Fayuvi
rebisufligene etisparvovec
Sources:FDA summary basis for approval ↗
Species
Mouse
Longest study
26 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Wild-type C57BL/6 mice only (6-month and 3-month GLP studies)
“which investigated the effect of a single intravenous administration of 5.0x1012 to 5.0x1013 vg/kg scAAV9.U1a.SGSH in WT C57Bl/6 mice.”
Why that species
Not stated in public reviews
Surrogate molecule
No surrogate; GLP studies used clinical vector (GMP Process A) in WT mice
“The definitive nonclinical Good Laboratory Practice (GLP) safety/biodistribution (BD) studies”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“No adverse vector-related findings were observed in the 6-month Good Laboratory Practice (GLP) safety and BD study”
Pivotal GLP studies
6-month GLP single IV study (5e12-5e13 vg/kg) and 3-month GLP single IV study (5e13-2e14 vg/kg) in WT C57BL/6 mice
“The definitive 3-month GLP safety and BD study investigated the effect of a single IV administration of 5.0x1013 to 2.0x1014 vg/kg FAYUVI in WT C57BL/6 mice.”
Route in tox
Intravenous
“single intravenous (IV) administration to wild type (WT) C57Bl/6 mice”
Skipped studiesopen answer page →
Genotoxicity
Not conducted; weight-of-evidence risk assessment used
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI.”
Carcinogenicity
Not conducted; weight-of-evidence risk assessment used
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI.”
Reproductive & developmental
Not conducted; weight-of-evidence risk assessment used
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI.”
Safety pharmacology
Not stated in public reviews
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
NOAEL 5.0x10^13 vg/kg (6-month) and 2.0x10^14 vg/kg (3-month); non-adverse, reversible clinpath/histopath findings
“The NOAEL was assigned at 2.0x1014 vg/kg.”
Risksopen answer page →
Immune & cytokine safety
Immunogenicity greater against AAV9 capsid than hSGSH transgene, proportional to dose
“Vector immunogenicity was greater against the AAV9 capsid versus the hSGSH transgene and was proportional to vector dose level.”
Biodistribution & persistence
Highest in liver; lower in brain; no vector-related gross or histopathologic findings
“Vector BD in brain was less than that of liver (highest) across dosed groups.”
Modality-specific risk
AAV9 high-dose safety (liver/immunogenicity); DART/genotox/tumorigenicity addressed by weight-of-evidence
“To address these concerns, the Applicant used a weight-of-evidence approach”