Adstiladrin
nadofaragene firadenovec · IFN-alpha2b (adenovirus, intravesical)Not conducted for rAd-IFN; conducted for excipient Syn3 only (Ames and chromosome aberration, negative)
Itvisma: genotox, carcinogenicity and repro: done or skipped?
onasemnogene abeparvovec (intrathecal) · SMN1 (AAV9, intrathecal)
Genotoxicity
Not conducted (single administration, known product characteristics, class safety profile)
“No carcinogenicity, genotoxicity, or repeat dosing were conducted for OAV101B.”
Carcinogenicity
Not conducted (single administration, known product characteristics, class safety profile)
“These studies are not necessary based on the intended ROA, dosing regimen (i.e., single infusion), known product characteristics, and overall safety profile for this class of product.”
Instead of carcinogenicity
Long-term follow-up studies capturing new malignancies and tumours under the risk management plan, instead of tumorigenicity studies
“Long-term follow-up studies that specifically include the occurrence of new malignancies and tumours as part of the risk management plan in place for OAV101. Therefore, tumorigenicity studies are not needed.”
Instead of genotoxicity
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.
DRG histopathology
Minor microscopic findings in DRG, spinal cord, peripheral nerves and brain at 6 weeks in NHP, without progression over 12 months
“These studies demonstrated that OAV101 was well tolerated at this dose level up to 12 months post injection, with minor microscopic findings reported 6 weeks post-administration in the dorsal root ganglia (DRG), spinal cord, peripheral nerves, and brain that did not increase in severity or incidence over the 12 month study.”
Reproductive & developmental
Mouse FEED (single IV OAV101B): no fertility effects, no germline transmission; mouse EFD NOAEL 1.1x10^14 vg/kg
“Fertility and early embryonic development (FEED) studies were conducted in healthy male and female FVB mice administered a single intravenous injection of OAV101B. There were no reported adverse effects on fertility, fecundity, or mating behaviors in either sex.”
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 (not necessary for a single-infusion product of this class)
“No carcinogenicity, genotoxicity, or repeat dosing were conducted for OAV101B. These studies are not necessary based on the intended ROA, dosing regimen (i.e., single infusion), known product characteristics, and overall safety profile for this class of product.”
Genotox: in vitro mammalian
Not conducted (not necessary for a single-infusion product of this class)
“No carcinogenicity, genotoxicity, or repeat dosing were conducted for OAV101B. These studies are not necessary based on the intended ROA, dosing regimen (i.e., single infusion), known product characteristics, and overall safety profile for this class of product.”
Genotox: in vivo
Not conducted (not necessary for a single-infusion product of this class)
“No carcinogenicity, genotoxicity, or repeat dosing were conducted for OAV101B. These studies are not necessary based on the intended ROA, dosing regimen (i.e., single infusion), known product characteristics, and overall safety profile for this class of product.”
Carcinogenicity model
Not conducted; not necessary given single infusion, known product characteristics and class safety profile
“No carcinogenicity, genotoxicity, or repeat dosing were conducted for OAV101B. These studies are not necessary based on the intended ROA, dosing regimen (i.e., single infusion), known product characteristics, and overall safety profile for this class of product.”
Carcinogenicity timing
Not conducted: not necessary (single infusion, known product characteristics, class safety profile)
“No carcinogenicity, genotoxicity, or repeat dosing were conducted for OAV101B. These studies are not necessary based on the intended ROA, dosing regimen (i.e., single infusion), known product characteristics, and overall safety profile for this class of product.”
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.
Same question, other gene therapies
Beqvez
fidanacogene elaparvovec · Factor IXNot conducted (classical); vector integration site analysis in dog and NHP liver instead
Casgevy
exagamglogene autotemcel · BCL11A enhancer (CRISPR-Cas9, ex vivo HSC)No conventional studies; specialized on-/off-target editing (GUIDE-seq, in silico, hybrid capture) and chromosomal aberration assessments
Elevidys
delandistrogene moxeparvovec · Micro-dystrophinNot conducted (low-frequency random AAV integration per literature)
Fayuvi
rebisufligene etisparvovec · SGSH (AAV9)Not conducted; weight-of-evidence risk assessment used
Genglycos
pariglasgene brecaparvovec · G6PC (AAV8)Not conducted (low AAV integration risk); vector integration assessed in germline transmission study
Glybera
alipogene tiparvovec · LPL (AAV1)Not conducted (standard tests not relevant); integration studies (LAM-PCR, nrLAM-PCR) instead
Hemgenix
etranacogene dezaparvovec · Factor IXNot conducted as standard battery; integration site analysis (LAM-PCR) in mouse and NHP liver showed low random integration
Imlygic
talimogene laherparepvec · GM-CSF (oncolytic HSV-1)Not conducted (ICH S6(R1))
Kebilidi
eladocagene exuparvovec · AADCNot conducted (agreed with CHMP; low integration risk in post-mitotic neurons)
Kresladi
marnetegragene autotemcel · ITGB2 (LVV, ex vivo HSC)Integration site analyses only (mouse and human transduced cells); no standard genotoxicity battery
Lenmeldy
atidarsagene autotemcel · ARSA (LVV, ex vivo HSC)Conducted: integration site analysis, in vitro immortalization assay, tumor-prone Cdkn2a-/- mouse; no insertional transformation
Luxturna
voretigene neparvovec · RPE65Not conducted (AAV low integration frequency; limited systemic exposure)
Lyfgenia
lovotibeglogene autotemcel · HBB T87Q (LVV, ex vivo HSC)Insertional mutagenesis assessed: in vitro immortalization (IVIM) assay and integration site analyses; low risk
Otarmeni
lunsotogene parvec · OTOF (AAV, intracochlear)Not conducted (low AAV insertional mutagenesis risk; limited distribution beyond inner ear)
Papzimeos
zopapogene imadenovec · HPV6/11 antigens (gorilla adenovirus)Not conducted (non-integrating, replication-incompetent adenovector; no insertional mutagenesis)
Roctavian
valoctocogene roxaparvovec · Factor VIIINot conducted (literature on AAV); NHP liver integration site analysis: 1.55x10^-3 IS/cell, no clonal expansion
Skysona
elivaldogene autotemcel · ABCD1 (LVV, ex vivo HSC)Standard genotox not relevant; insertional mutagenesis assessed by in vitro immortalization assay and integration site analysis
Strimvelis
autologous CD34+ cells transduced with ADA (no INN) · ADA (gamma-retroviral, ex vivo HSC)Not conducted (conventional assays cannot detect insertional events)
Tudriqev
vusolimogene oderparepvec · GALV-GP + GM-CSF (oncolytic HSV-1)Not conducted (not warranted based on product characteristics and safety profile)
Vyjuvek
beremagene geperpavec · COL7A1 (HSV-1, topical)Not conducted (HSV-1 does not integrate; negligible insertional mutagenesis)
Waskyra
etuvetidigene autotemcel · WAS (LVV, ex vivo HSC)Conventional mutagenicity not conducted; IVIM assay, vector insertion site analysis and VITA performed, no genotoxic potential
Zevaskyn
prademagene zamikeracel · COL7A1 (RV-modified keratinocyte sheets)Not conducted (integration site analysis in transduced RDEB keratinocytes instead; no clonality or oncogene preference)
Zolgensma
onasemnogene abeparvovec · SMN1Not conducted (low random rAAV integration per literature)
Zynteglo
betibeglogene autotemcel · HBB T87Q (LVV, ex vivo HSC)Insertional mutagenesis assessed instead of standard genotox: in vitro immortalization assay (low potential) and integration site analysis (no clonal dominance)