Adstiladrin
nadofaragene firadenovec · IFN-alpha2b (adenovirus, intravesical)Not conducted for rAd-IFN; conducted for excipient Syn3 only (Ames and chromosome aberration, negative)
Beqvez: genotox, carcinogenicity and repro: done or skipped?
fidanacogene elaparvovec · Factor IX
Genotoxicity
Not conducted (classical); vector integration site analysis in dog and NHP liver instead
“Based on the IS profile, genotoxicity from vector integration appears to be a low risk.”
Carcinogenicity
Not conducted (not warranted given product characteristics, BD/tox data, population)
“Studies to evaluate the safety pharmacology, developmental and reproductive toxicity, and carcinogenicity/tumorigenicity of BEQVEZ were not conducted.”
Reproductive & developmental
Not conducted (male-only population); rabbit semen shedding/germline study only
“This reviewer agrees that the omission of dedicated embryo-fetal development studies and pre- and postnatal development studies is acceptable.”
Safety pharmacology
Not conducted
“No safety pharmacology studies with BEQVEZ were conducted.”
Same question, other gene therapies
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))
Itvisma
onasemnogene abeparvovec (intrathecal) · SMN1 (AAV9, intrathecal)Not conducted (single administration, known product characteristics, class safety profile)
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)