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
The reviews list the species but not why. For biologics, ICH S6(R1) asks for species in which the product is pharmacologically active (target binding and activity), usually a cynomolgus monkey.
“A relevant species is one in which the test material is pharmacologically active due to the expression of the receptor or an epitope (in the case of monoclonal antibodies).”
✓ VerifiedICH 2011: ICH S6(R1): Preclinical Safety Evaluation of Biotechnology-Derived…, p. 7Source ↗
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”
Species: general tox
Wild-type C57BL/6 mouse only (3-month and 6-month GLP single-dose IV studies)
“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.”
Species: DART
Not conducted; addressed by weight-of-evidence risk assessment
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI.”
Species: carcinogenicity
Not conducted; addressed by weight-of-evidence risk assessment
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI.”
Surrogate used in
No surrogate used; GLP safety/biodistribution studies used clinical FAYUVI (GMP Process A)
“The definitive nonclinical Good Laboratory Practice (GLP) safety/biodistribution (BD) studies and all clinical trials (Nos. ABT-001, ABT-003, and LTFU-ABO-102) were conducted with FAYUVI manufactured under GMP conditions via Process A.”
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.”
Instead of carcinogenicity
Weight-of-evidence risk assessments integrating a literature review, FAYUVI toxicology data and historical data from other AAV products
“assessments that integrated a literature review, FAYUVI toxicology data, and historical data from other AAV products.”
DRG histopathology
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
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
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Genotox: Ames
Not conducted
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI.”
Genotox: in vitro mammalian
Not conducted
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI.”
Genotox: in vivo
Not conducted
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI.”
Carcinogenicity model
Not conducted; weight-of-evidence risk assessment instead
“To address these concerns, the Applicant used a weight-of-evidence approach”
Carcinogenicity timing
Not conducted: carcinogenicity/tumorigenicity addressed by weight-of-evidence approach
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI. To address these concerns, the Applicant used a weight-of-evidence approach”
hERG / QT
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Fayuvi don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.
How it's usually set for gene therapies
FDA expects preclinical proof-of-concept and toxicology studies to identify active dose levels and support the choice of starting dose and escalation. The 2013 guidance gives no numeric formula or scaling rule for the starting dose.
“Selection of potential starting dose level, dose-escalation schedule, and dosing regimen for clinical trials.”
✓ VerifiedFDA 2013: Preclinical Assessment of Investigational Cellular and Gene Therapy…, p. 7Source ↗
This product's starting point
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 (FDA summary basis for approval, p. 11)
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”
Anti-drug antibodies: animals
Dose-proportional immune responses in mice, greater against AAV9 capsid than hSGSH transgene
“Vector immunogenicity was greater against the AAV9 capsid versus the hSGSH transgene and was proportional to vector dose level.”
Anti-drug antibodies: patients
All patients seroconverted to anti-AAV9 antibodies and all had increased serum anti-SGSH antibodies
“All patients seroconverted to anti-AAV9 antibody positive following administration of FAYUVI . All patients had an increase in anti-SGSH antibodies in serum following administration of FAYUVI .”
Tox packageopen answer page →
Before first-in-human
First-in-human: where
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Repeat-dose tox before first-in-human
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
First-in-human starting dose
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Fayuvi don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.
How it's usually set for gene therapies
FDA expects preclinical proof-of-concept and toxicology studies to identify active dose levels and support the choice of starting dose and escalation. The 2013 guidance gives no numeric formula or scaling rule for the starting dose.
“Selection of potential starting dose level, dose-escalation schedule, and dosing regimen for clinical trials.”
✓ VerifiedFDA 2013: Preclinical Assessment of Investigational Cellular and Gene Therapy…, p. 7Source ↗
This product's starting point
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 (FDA summary basis for approval, p. 11)
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
No repeat-dose study (single administration); longest is 6-month GLP single IV mouse study
“No adverse vector-related findings were observed in the 6-month Good Laboratory Practice (GLP) safety and BD study, which investigated the effect of a single intravenous administration”
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.”
DART package
Species: DART
Not conducted; addressed by weight-of-evidence risk assessment
“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.”
PPND / ePPND: when
Not conducted: DART replaced by weight-of-evidence approach
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI. To address these concerns, the Applicant used a weight-of-evidence approach”
Carcinogenicity
Species: carcinogenicity
Not conducted; addressed by weight-of-evidence risk assessment
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI.”
Carcinogenicity model
Not conducted; weight-of-evidence risk assessment instead
“To address these concerns, the Applicant used a weight-of-evidence approach”
Carcinogenicity timing
Not conducted: carcinogenicity/tumorigenicity addressed by weight-of-evidence approach
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI. To address these concerns, the Applicant used a weight-of-evidence approach”
Safety marginopen answer page →
Safety margin at NOAEL
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
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.”
Efficacy evidenceopen answer page →
Efficacy evidence
MPS IIIA mouse pharmacology study (survival, brain GAG, Morris water maze, GFAP, neuropathology); SGSH knock-out cells in vitro
“The minimum effective dose level of 5.0x1012 vg/kg was identified in the definitive pharmacology study conducted in mice based on survival, brain glycosaminoglycan (GAG) concentration, Morris water maze performance, reduced brain glial fibrillary acidic protein (GFAP) , and improved neuropathology.”
Why that model
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Reviewer's view of the efficacy data
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Test articleopen answer page →
Test article vs clinical lot
Definitive GLP safety and biodistribution studies and all clinical trials used FAYUVI manufactured under GMP conditions via Process A. Bridging: In vivo pharmacology studies bridged in vivo potency between the clinical Process A material and the later manufacturing process
“The definitive nonclinical Good Laboratory Practice (GLP) safety/biodistribution (BD) studies and all clinical trials (Nos. ABT-001, ABT-003, and LTFU-ABO-102) were conducted with FAYUVI manufactured under GMP conditions via Process A.”
Vector and route
scAAV9.U1a.SGSH, single intravenous administration
“No adverse vector-related findings were observed in the 6-month Good Laboratory Practice (GLP) safety and BD study, 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.”
First approval
2026 (FDA)
“Summary Basis for Regulatory Action Date: September 17, 2026”
Flexibilityopen answer page →
Flexibility accepted
CarcinogenicityVerdict not stated
No genotoxicity or carcinogenicity/tumorigenicity studies; weight-of-evidence risk assessment instead
Why: Concerns addressed by a weight-of-evidence approach instead of dedicated studies · Weight of evidence
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI. To address these concerns, the Applicant used a weight-of-evidence approach”
DARTVerdict not stated
No developmental and reproductive toxicity studies; weight-of-evidence risk assessment instead
Why: Concerns addressed by a weight-of-evidence approach instead of dedicated studies · Weight of evidence
“Developmental and reproductive toxicity (DART), genotoxicity, and carcinogenicity/tumorigenicity studies were not conducted with FAYUVI. To address these concerns, the Applicant used a weight-of-evidence approach”
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